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When a new molecular entity is predicted to exhibit high clearance in humans, pharmaceutical sponsors almost universally search for similar acting back-up compounds that will demonstrate low clearance. Here we show that, except for oral dosing, there can be marked advantages to developing and commercializing controlled release formulations of high clearance drugs, the expertise of readers of this journal. Our recent publications demonstrate that the universally held pharmacokinetic principle that drug delivery rate has no effect on measured drug clearance is not correct. Rather, we show that if clearance from the drug delivery site is markedly less than the iv bolus clearance of a drug, the in vivo drug clearance can be the drug delivery clearance controlled by the designed dosage form. This approach will be especially advantageous for high hepatic clearance drugs. These advantages include not being concerned with: a) saturable nonlinear kinetics, b) significant pharmacogenomic differences, c) drug-drug induction mechanisms, and d) in many cases drug-drug inhibition interactions. This is due to the ability of a drug sponsor to design clearance, independent of the pharmacokinetic characteristics for high clearance compounds, where clearance from the dosage form becomes the drug clearance from the patient. Recognition of this principle, as described here, results from our development of the use of Kirchhoff's Laws from physics to derive rate-defining clearance and rate constant elimination processes independent of differential equation derivations. The key message for readers of this journal is that high clearance drugs are potentially drugable through formulation design and should not be outright disregarded, since for such drugs the dose-corrected area under the curve can be increased if the release rate from the injection site is controlled and slow resulting in drug clearance from the body controlled by clearance from the dosage form. The concepts presented here describe previously unrecognized advantages of controlled release formulations.

Methane is a major contributor to anthropogenic greenhouse gas emissions. Identifying large sources of methane, particularly from the oil and gas sectors, will be essential for mitigating climate change. Aircraft-based methane sensing platforms can rapidly detect and quantify methane point-source emissions across large geographic regions, and play an increasingly important role in industrial methane management and greenhouse gas inventory. We independently evaluate the performance of five major methane-sensing aircraft platforms: Carbon Mapper, GHGSat-AV, Insight M, MethaneAIR, and Scientific Aviation. Over a 6 week period, we released metered gas for over 700 single-blind measurements across all five platforms to evaluate their ability to detect and quantify emissions that range from 1 to over 1,500 kg(CH4)/h. Aircraft consistently quantified releases above 10 kg(CH4)/h, and GHGSat-AV and Insight M detected emissions below 5 kg(CH4)/h. Fully blinded quantification estimates for platforms using downward-facing imaging spectrometers have parity slopes ranging from 0.76 to 1.13, with R2 values of 0.61 to 0.93; the platform using continuous air sampling has a parity slope of 0.5 (R2 = 0.93). Results demonstrate that aircraft-based methane sensing has matured since previous studies and is ready for an increasingly important role in environmental policy and regulation.

Due to the increase in severe consequences of mild steel corrosion, the development of coatings with improvement in corrosion-resistant properties has become very essential. In this work, benzotriazole (BTA) was encapsulated into halloysite nanotubes (HNTs) for inhibiting the corrosion of mild steel surface. The BTA-encapsulated HNT exhibits pH-responsive properties over a wide range of pH. It was found that a large amount of BTA was released at pH 3 (48 %), followed by pH 7 (30 %) and least in the case of pH 10 (20 %). At neutral pH, a rapid release of BTA was observed during initial exposure, reaching a steady-state later, with no significant release further. A salt immersion test was carried out after immersing mild steel (MS) substrates in BTA-HNT nanopowder dispersion in 3.5 wt% NaCl at different pH. SEM images and EDS maps confirmed that corrosion product formation on MS surface at pH 3 was significantly more with corrosion pits along with HNTs throughout the surface. At pH 7 and 10, corrosion pits were observed with very few halloysite nanotubes on the surface. An optimum amount of BTA is required to inhibit corrosion, excessive release may cause more Cl− ions to penetrate, leading to more corrosion. Electrochemical data also reveals the same trend, where the i corr value was maximum for pH 3 (1.09 × 10−5 A/cm2) > pH 7 (4.74 × 10−6 A/cm2) > pH 10 (3.43 × 10−6 A/cm2). Therefore, results suggest that BTA-encapsulated HNT can be efficiently incorporated into the coating matrix for their controlled release to provide corrosion protection under varying neutral and alkaline marine environments. [Display omitted] [ABSTRACT FROM AUTHOR]

Drug-loaded polymeric micelles have proven to be highly effective carrier systems for the efficient delivery of hydrophobic photosensitizers (PSs) in photodynamic therapy (PDT). This study introduces the micellization potential of poly(oligoethylene glycol methyl ether methacrylate) (pOEGMA) as a novel approach, utilizing the hydrophobic methacrylate segments of pOEGMA to interact with highly hydrophobic zinc phthalocyanine (ZnPc), thereby forming a potential micellar drug carrier system. The ZnPc molecule was synthesized from phthalonitrile derivatives and its fluorescence, photodegradation, and singlet oxygen quantum yields were determined in various solvents. In solvents such as tetrahydrofuran, dimethyl sulfoxide, and N,N-dimethylformamide, the ZnPc compound exhibited the requisite photophysical and photochemical properties for PDT applications. The pOEGMA homopolymer was synthesized via reversible addition-fragmentation chain-transfer polymerization, while ZnPc-loaded pOEGMA micelles were prepared using the nanoprecipitation method. Characterization of the pOEGMA, ZnPc, and micelles was conducted using FTIR, 1H-NMR, dynamic light scattering, matrix-assisted laser desorption/ionization time-of-flight mass spectrometries, gel permeation chromatography, and transmission electron microscopy. The critical micelle concentration was determined to be 0.027 mg ml−1 using fluorescence spectrometry. The drug loading and encapsulation efficiencies of the ZnPc-loaded micelles were calculated to be 0.67% and 0.47%, respectively. Additionally, the release performance of ZnPc from pOEGMA micelles was monitored over a period of nearly 10 d, while the lyophilized micelles exhibited stability for 3 months. Lastly, the ZnPc-loaded micelles were more biocompatible than ZnPc on L929 cell line. The results suggest that the pOEGMA homopolymer possesses the capability to micellize through its methacrylate segments when interacting with highly hydrophobic molecules, presenting a promising avenue for enhancing the delivery efficiency of hydrophobic PSs in PDT. Moreover, it was also deciphered that obtained formulations were highly biocompatible according to cytotoxicity results and could be safely employed as drug delivery systems in further applications. [ABSTRACT FROM AUTHOR]

Sodium chlorite (NaClO2) is a new type of air disinfectant, which can oxidize formaldehyde into carbon dioxide (CO2) on account of releasing chlorine dioxide (ClO2) gas under acidic condition. Unfortunately, NaClO2 is prone to moisture absorption and decomposition when exposed to air. In this paper, NaClO2 was microencapsulated based on emulsion crosslinking method for improving its stability and controlled release properties. Due to their high biocompatibility, sodium alginate (SA) and sodium carboxymethyl cellulose (CMC‐Na) were selected as the wall material to prepare NaClO2‐SA/CMC‐Na composite microcapsules. The results showed that mean particle size of NaClO2‐SA/CMC‐Na composite microcapsules was about 225 nm, and their encapsulation ratio was up to 73.18%. In addition, the thermal stability and environmental tolerance of NaClO2 are improved greatly through microencapsulating. It was proved by formaldehyde degradation testing that the efficiency of formaldehyde degradation using resulted samples can continue to increase after seven days in pH 6.5 environment, indicating their good controlled‐release performance. Moreover, degradation efficiency on 30 µg/mL formaldehyde solution using the resulted microcapsules is up to 97.08%. Meanwhile, after 20 repetition degradation, NaClO2‐SA/CMC‐Na composite microcapsules can still continuously degrade formaldehyde gas. Therefore, NaClO2‐SA/CMC‐Na composite microcapsules reveal good stability and prolonged action on formaldehyde degradation. [ABSTRACT FROM AUTHOR]

Percutaneous coronary intervention (PCI) is currently the main method for treating coronary artery stenosis, but the incidence of restenosis after PCI is relatively high. Restenosis, the narrowing of blood vessels by more than 50% of the normal diameter after PCI, severely compromises the therapeutic efficacy. Therefore, preventing postinterventional restenosis is important. Vascular restenosis is mainly associated with endothelial injury, the inflammatory response, the proliferation and migration of vascular smooth muscle cells (VSMCs), excessive deposition of extracellular matrix (ECM) and intimal hyperplasia (IH) and is usually prevented by administering antiproliferative or anti-inflammatory drugs through drug-eluting stents (DESs); however, DESs can lead to uncontrolled drug release. In addition, as extracorporeal implants, they can cause inflammation and thrombosis, resulting in suboptimal treatment. Therefore, there is an urgent need for a drug carrier with controlled drug release and high biocompatibility for in vivo drug delivery to prevent restenosis. The development of nanotechnology has enabled the preparation of nanoparticle drug carriers with low toxicity, high drug loading, high biocompatibility, precise targeting, controlled drug release and excellent intracellular delivery ability. This review summarizes the advantages of nanoparticle drug carriers for treating vascular restenosis, as well as how nanoparticles have improved targeting, slowed the release of therapeutic agents, and prolonged circulation in vivo to prevent vascular restenosis more effectively. The overall purpose of this review is to present an overview of nanoparticle therapy for vascular restenosis. We expect these findings to provide insight into nanoparticle-based therapeutic approaches for vascular restenosis. [ABSTRACT FROM AUTHOR]

Background: Globally, prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) is increasing, and there is an urgent need to develop innovative therapies that promote liver regeneration following hepatectomy for this disease. Surgical excision is a key therapeutic approach with curative potential for liver tumors. However, hepatic steatosis can lead to delayed liver regeneration and higher post-operative complication risk. Mesenchymal stem cells-conditioned medium (MSC-CM) is considered a rich source of paracrine factors that can repair tissues and restore function of damaged organs. Meanwhile, hydrogels have been widely recognized to load MSC secretome and achieve sustained release. This study aimed to evaluate the therapeutic effect of hydrogel-encapsulated MSC-CM on liver regeneration following partial hepatectomy (PHx) in a rodent model of diet-induced hepatic steatosis. Methods: Male Lewis rats were fed with a methionine and choline–deficient diet. After 3 weeks of feeding, PHx was performed and rats were randomly allocated into two groups that received hydrogel-encapsulated MSC-CM or vehicle via the intra-mesenteric space of the superior mesenteric vein (SMV). Results: The regeneration of the remnant liver at 30 and 168 h after PHx was significantly accelerated, and the expressions of proliferating cell nuclear antigen were significantly enhanced in the MSC-CM group. MSC-CM treatment significantly increased hepatic ATP and β-hydroxybutyrate content at 168 h after PHx, indicating that MSC-CM fosters regeneration not only in volume but also in functionality. The number of each TUNEL- and cleaved caspase-3 positive nuclei in hepatocytes at 9 h after PHx were significantly decreased in the MSC-CM group, suggesting that MSC-CM suppressed apoptosis. MSC-CM increased serum immunoregulatory cytokine interleukin-10 and interleukin-13 at 30 h after PHx. Additionally, mitotic figures and cyclin D1 expression decreased and hepatocyte size increased in the MSC-CM group, implying that this mode of regeneration was mainly through cell hypertrophy rather than cell division. Conclusions: MSC-CM represents a novel therapeutic approach for patients with MASLD requiring PHx. [ABSTRACT FROM AUTHOR]

Bone-related disorders create critical-sized bone defects that require multifunctional bone graft materials for successful bone repair. Integration of therapeutics with 3D-printed calcium phosphate (CaP) scaffolds offers a personalized treatment option. The inherent properties of CaP enable it to act as a bone substitute, while drug delivering abilities provide a new dimension through localized drug delivery. It enhances both therapeutic efficacy and patient compliance. Controlled delivery of drugs significantly impacts the process of bone regeneration. It can be achieved through various strategies, including polymer coatings, formulation integration, microporous scaffold design, chemical crosslinking, and direct extrusion 3D printing. Understanding drug release mechanisms aids in assessing the in vivo performance of multifunctional scaffolds. 3D printing has revolutionized bone tissue engineering (BTE) by enabling the fabrication of patient- or defect-specific scaffolds to enhance bone regeneration. The superior biocompatibility, customizable bioactivity, and biodegradability have enabled calcium phosphate (CaP) to gain significance as a bone graft material. 3D-printed (3DP) CaP scaffolds allow precise drug delivery due to their porous structure, adaptable structure–property relationship, dynamic chemistry, and controlled dissolution. The effectiveness of conventional scaffold-based drug delivery is hampered by initial burst release and drug loss. This review summarizes different multifunctional drug delivery approaches explored in controlling drug release, including polymer coatings, formulation integration, microporous scaffold design, chemical crosslinking, and direct extrusion printing for BTE applications. The review also outlines perspectives and future challenges in drug delivery research, paving the way for next-generation bone repair methodologies. [ABSTRACT FROM AUTHOR]

Acyclovir (ACY) is used to treat oral viral herpes but has low solubility and bioavailability. Stearic acid (SA) is lipophilic and can be combined with drugs. Therefore, this study aimed to characterize the properties of SA nanoparticles in increasing the cellular uptake of ACY by oral epithelial cells. The hypothesis was that SA nanoparticles increase sustained ACY release, are stable, and increase drug uptake. The production parameters (duration and amplitude of sonication) were optimized to produce solid lipid nanoparticles (SLN) of SA-containing ACY. Particle stability was characterized under different storage conditions (4 °C and 37 °C for 1, 15, and 45 days). SLN were further characterized for their pharmacokinetic profile, cytotoxicity, in vitro permeability, and ability to modulate gene expression and promote ACY uptake by oral epithelial cells. Pharmacokinetic studies revealed sustained and diffusional release of ACY from the SLN, with an initial burst release of 15 min. After 45 d of storage, SLN kept at both 4 °C and 37 °C showed a maximum release of > 90 % of the drug at 120 min. Cells treated with SLN presented a significantly higher intracellular drug content than those treated with ACY and significantly increased the genetic expression of TJP-1 , OCLN , and ECAD. The hypothesis was accepted as SA nanoparticles containing ACY can sustain drug delivery and enhance its absorption into epithelial cells. Therefore, SA nanoparticles are promising for improving ACY uptake in treating oral herpes and other infections caused by HSV-1. [ABSTRACT FROM AUTHOR]

The development of new materials for the controlled release of molecules represents a topic of primary importance in medicine, as well as in food science. In recent years, eutectic solvents have been applied as releasing media due to their improved capacity to interact with specific molecules, offering a broad range of tunability. Nevertheless, their application in essential oil dissolution are rare and more data are needed to develop new generations of effective systems. Herein, three eutectic systems, respectively, composed of choline chloride and ethylene glycol (1:2 molar ratio), methyltriphenylphosphonium bromide and ethylene glycol (molar ratio 1:5), and choline chloride and glycerol (molar ratio 1:1.5) were tested as materials for the controlled release of an essential oil derived from Citrus lemon leaves. Through static headspace fractionation, followed by gas chromatographic analysis, the performances of the three systems were assessed. The specific composition of DESs was pivotal in determining the releasing polar molecules as aldehydes and alcohols. A sustainability ranking based on the EcoScale tool highlighted the superior characteristics of the choline chloride–glycerol DES. [ABSTRACT FROM AUTHOR]

Novel thiomer/nanoclay nanocomposites based on a thiomer and montmorillonite (MMT) were prepared in order to obtain a mucoadhesive material with controlled release properties for its potential use as drug carrier. The thiomer was synthesized by immobilization of L-cysteine in alginate mediated by carbodiimide reaction and further characterized by FT-IR and Ellman's reaction. Nanocomposites with growing concentrations of thiomer and MMT were prepared and analyzed by XRD, TGA and TEM. Rheological behavior of nanocomposite in contact with mucin and intestinal mucus were studied as in vitro and in situ mucoadhesion approach, showing until ∼10-fold increasing in the complex viscosity and ∼27-fold in elastic modulus when the amount of thiomer is increased. Higuchi and Korsmeyer-Peppas kinetic models were evaluated in order to study the release of deltamethrin from nanocomposite films. Release profiles showed a retard in the migration of the drug influenced by the amount of MMT (P < 0.05). Diffusion coefficient (D) showed a significant decrease (P < 0.0001) when concentration of MMT is increased reaching D = 4.18 × 10–7 m2 h–1, which resulted ∼7-fold lower in comparison with formulation without MMT. This hybrid nanocomposite can be projected as a potential mucoadhesive drug carrier with controlled release properties. [Display omitted] • Mucoadhesive nanocomposites based on a thiomer and montmorillonite was prepared. • Alginate was functionalized with L-cysteine showing 186.0 µmol –SH/g polymer. • XRD and TEM indicate intercalated forms for nanocomposites. • Mucoadhesion assay showed strong interaction between nanocomposite and mucin/mucus. • Higuchi and Korsmeyer-Peppas model satisfied release process with high R 2. • Nanocomposite present a controlled release depending the amount of MMT. [ABSTRACT FROM AUTHOR]

Inulin, a naturally occurring polysaccharide derived from plants such as chicory root, has emerged as a significant ingredient in pharmaceutical sciences due to its diverse therapeutic and functional properties. This review explores the multifaceted applications of inulin, focusing on its chemical structure, sources, and mechanisms of action. Inulin's role as a prebiotic is highlighted, with particular emphasis on its ability to modulate gut microbiota, enhance gut health, and improve metabolic processes. The review also delves into the therapeutic applications of inulin, including its potential in managing metabolic health issues such as diabetes and lipid metabolism, as well as its immune-modulating properties and benefits in gastrointestinal health. Furthermore, the article examines the incorporation of inulin in drug formulation and delivery systems, discussing its use as a stabilizing agent and its impact on enhancing drug bioavailability. Innovative inulin-based delivery systems, such as nanoparticles and hydrogels, are explored for their potential in controlled release formulations. The efficacy of inulin is supported by a review of clinical studies, underscoring its benefits in managing conditions like diabetes, cardiovascular health, and gastrointestinal disorders. Safety profiles, regulatory aspects, and potential side effects are also addressed. This comprehensive review concludes with insights into future research directions and the challenges associated with the application of inulin in pharmaceutical sciences. [ABSTRACT FROM AUTHOR]

The development of polymer carriers for systems of prolonged and controlled release of substances, particularly drugs, into the action environment is a relevant task in polymer chemistry and technology. This aims to solve the problem of reducing the effective dose of a medical drug administered into the body of a person or animal. The latest achievements in the field of creating such carriers in the form of spherical particles based on 2- hydroxyethyl methacrylate and polyvinylpyrrolidone (co)polymers are analyzed and summarized. The working principles and advantages of such systems are described. The research of the synthesis regularities, structure, properties and perspectives of application of granular hydrogels based on 2-hydroxyethyl methacrylate and its copolymers with polyvinylpyrrolidone was analyzed. The mixture of decanol and cyclohexanol as a solvent for the monomer phase is substantiated. Based on the analysis of kinetic studies, the optimal technological parameters for the suspension polymerization of 2-hydroxyethyl methacrylate with polyvinylpyrrolidone were selected, and the possibility of regulating the dispersion characteristics of copolymers via changes in the technological synthesis modes was confirmed. The results of studies on the sorption-desorption properties of copolymers concerning model substances and drugs are described. The possibility of directed regulation of sorption capacity and drug release rate through changes in copolymer composition was confirmed. Methods for increasing the sorption capacity of hydrogels for drugs are proposed. [ABSTRACT FROM AUTHOR]

Polymer-modified fertilizers (PMFs) with prolonged nutrient release present a promising solution to address the challenges associated with conventional fertilization practices, particularly for sensitive crops such as strawberries. This study investigates the effectiveness of biodegradable PMFs in maintaining nutrient availability at optimal levels while minimizing root burn and nutrient losses. In a factorial field experiment, we obtaineda total of 3780 sets of parallel measured time series for soil EC, moisture, and temperature as well as two sets of harvest data to evaluate the impact of varying concentrations of polyvinyl alcohol (PVA) on the nutrient release rates from complex NPK fertilizer and monoammonium phosphate. Results indicate that polymer modifications significantly slow down nutrient release, leading to optimal salt levels and maximizing yield while remaining low enough to prevent the risk of root burn (EC of soil solution below 1 mS/cm). Consequently, the application of PMFs enhances strawberry yield surplus (on average 2.8 times in the second harvest) by ensuring a steady supply of nutrients throughout the growing season without inducing stress, which reduces the yield by nearly half. This research provides valuable insights into the development of more effective fertilization strategies for strawberry cultivation and other sensitive crops using PMFs. [ABSTRACT FROM AUTHOR]

Essential oils extracted from natural plants can serve as safe food additives, compared with conventional chemical or synthetic additives. Essential oils have also been incorporated into food packaging materials to impart their bacteriostatic and antioxidant properties. Among them, thymol (THY), a monoterpene phenolic compound extracted from the thyme plant, has been used as a bacteriostatic agent in active packaging materials with functional properties, due to its significant bacteriostatic properties. However, the activity of highly volatile THY is easily affected by the packaging environment. Therefore, appropriate techniques are needed to incorporate the THY into polymer matrices, in order to improve its stability and utilization for controlled release. This study aims to prepare the potato starch films of active packaging, taking the mesoporous nano-silica (mobil composition of matter No. 41, MCM-41) as the controlled-release carrier of THY (THY-MCM-41), potato starch as the film-forming substrate, glycerol as the plasticizer, and calcium chloride as the cross-linking agent. Single-factor experiments were carried out to determine the suitable additive ranges of potato starch, glycerol, calcium chloride, and THY-MCM-41 mass concentration in the packaging film. The L9 (34) orthogonal test was also implemented to investigate the interactive effects of potato starch, glycerol, calcium chloride, and THY-MCM-41 on the thickness, opacity, moisture absorption (MA), water vapor permeability (WVP), tensile strength (TS), and elongation at break (EB) of the packaging film. The optimal conditions were obtained to prepare the potato starch films of active packaging. A systematic investigation was made to clarify the THY release kinetics in the optimal combination of packaging film at different temperatures and relative humidity (RH) environments. A prediction model of THY release was constructed to optimize the THY. The results showed that the optimal properties of the prepared packaging film A were achieved in the TS, MA, WVP, oxygen permeability (OP) and opacity were 7.16 MPa, 89.23%, 1.42 × 10-10 g/(m·s·Pa), 1.02 × 10-15 cm²/s·Pa, and 1.16 mm-1, respectively, when the mass concentrations of potato starch, glycerol, calcium chloride and THY-MCM-41 were 0.04, 0.015, 0.005, and 0.005 g/mL, respectively. Scanning electron microscope (SEM) and Fourier-transformed infrared (FTIR) spectroscopy confirmed that the denser and more uniform microstructure of packaging film was observed, where THY-MCM-41 was uniformly dispersed in the potato starch film, indicating better compatibility with potato starch. Thermogravimetric (TG) analysis showed that the encapsulation of MCM-41 improved the stability of THY in the potato starch film. In addition, the release kinetics of THY in the potato starch film of active packaging demonstrated that the initial explosive release was shifted to a subsequent sustained release under different temperature-RH environments. The active packaging film was prepared to effectively control the release rate of THY for the effective time of THY up to 10d. The release pattern of THY was in accordance with the First-order release model (R² > 0.980), and the release index “n” was less than 0.5, indicating that the release behavior of THY followed Fickian diffusion law. This finding can also provide the theoretical foundation for the precise release of active substances in the development of active packaging films. [ABSTRACT FROM AUTHOR]

In this study, the synthesis and characterization of poly(ethyl methacrylate‐co‐acrylamide) (i.e., poly(EMA‐co‐AAm)) nanogels and the loading and release studies of doxorubicin hydrochloride were carried out. The synthesis of nanogels was carried out using the emulsion polymerization technique at 60 °C. Swelling experiments showed that the nanogels were sensitive to temperature and pH of the medium. Zeta sizer analysis results showed that the synthesized nanogels had an average size of 23.17 nm and the PDI value was 0.270. In the loading studies of doxorubicin into nanogels, the drug loading capacity (DLC) of the nanogel was determined as 32% and the drug loading efficiency (DLE) was determined as 77%. Release studies conducted at pH = 5.4 and pH = 7.4 at 37 °C showed that the release percentage was 17% even in 32 h at pH = 7.4, and 82% in 5 h at pH = 5.4. Release studies conducted at different temperatures at pH = 5.4 revealed that the release percentage was 82% at 37 °C, 85% at 39 °C, and 89% at 41 °C. These results revealed that poly(EMA‐co‐AAm) nanogels can be used in targeted controlled release of doxorubicin and can increase drug effects while reducing side effects. [ABSTRACT FROM AUTHOR]

Colloidosomes, pioneering microcapsules composed of coagulated colloidal particles assembled at the interface of emulsion droplets, have garnered significant attention due to their remarkable properties and potential applications in targeted and controlled drug delivery. Their unique core-shell architecture offers unparalleled advantages, including tunable permeability, mechanical strength and encapsulation capabilities for a wide range of therapeutic agents. These versatile carriers have demonstrated remarkable potential in delivering small molecules, biomacromolecules, genetic materials and even living cells, addressing challenges associated with conventional drug delivery systems. Colloidosomes can be fabricated through various techniques, encompassing emulsion-based, nature-of-colloids-based and emerging methods such as microfluidics and 3D printing. Comprehensive characterization, employing techniques like electron microscopy, spectroscopy and rheology, is crucial for understanding their structural, physical and functional properties. Remarkable advancements have been achieved in developing stimuli-responsive, targeted and multi-functional colloidosomes, enabling precise spatiotemporal control, selective accumulation and integrated functionalities for theranostic applications. Despite their immense potential, challenges remain in scaling up production, ensuring long-term stability, navigating regulatory landscapes and facilitating clinical translation. Addressing these obstacles through collaborative efforts, advanced characterization and the integration of emerging technologies is paramount for unlocking the full potential of colloidosomes in revolutionizing drug delivery strategies and realizing personalized medicine. [ABSTRACT FROM AUTHOR]

Background: The SARS-CoV-2 pandemic has highlighted niclosamide (NIC) as a promising treatment for COVID-19. However, its clinical application is limited due to its poor water solubility, resulting in low bioavailability. Methods: To address this issue, we developed a AuNP-HA-NIC system, which combines gold nanoparticles with hyaluronic acid to enhance drug delivery. Our comprehensive characterization of the system revealed that hyaluronic acid with specific molecular weights, particularly those exposed to electron-beam irradiation between 2 and 20 kGy, produced the most stable nanoparticles for efficient drug loading and delivery. Results: Additionally, the AuNP-HA-NIC system exhibits a significant sensitivity to pH changes, which is a critical feature for targeted drug release. Under acidic conditions mimicking the stomach and small intestine, minimal drug release was observed, indicating the effective prevention of premature drug release in the gastrointestinal tract. Furthermore, the integration of a targeting aptamer established specific binding abilities towards the SARS-CoV-2 spike protein, distinguishing it from other coronaviruses. Conclusions: As research progresses, and with further in vivo testing and optimization, the AuNP-HA-NIC–aptamer system holds great promise as a game-changer in the field of antiviral therapeutics, particularly in the battle against COVID-19. [ABSTRACT FROM AUTHOR]

In this work, five different dextran-based cryogels for controlled drug release are investigated. Vitamin B12 was used as a model drug for in vitro release tests. Two different drug-loading procedures were adopted, leading to very different drug release curves. Indeed, a fast Fickian release was observed when freeze-dried samples of DEX40PEG360MA and DEX40PEG500MA were infused with the drug after cryogel formation. On the contrary, a slowed highly non-Fickian behavior arises when the drug is loaded before the low-temperature crosslinking step, leading to the cryogel formation. The non-Fickian drug release, observed for all the five different dextran-based cryogels investigated, is actually due to the cryoconcentration phenomenon, modeled with a two-step release process. The proposed transport model accurately predicts experimental release curves characterized by a long lag time, confirming that dextran-based cryogels are suitable for controlled release. [ABSTRACT FROM AUTHOR]

Loading effective ingredients of pesticides into suitable carriers and modifying drug-loaded particles to achieve the functions of targeted delivery, controlled release, etc, can enhance the efficacy and utilization of pesticides, prolonging their duration, and reduce side effects. Metal-organic frameworks (MOFs) have received wide attention in the field of pesticide loading due to their unique structural and functional characteristics. Among them, ZIF-8 (zeolitic imidazolate framework-8) is an excellent material in the ZIF series, characterized by its high BET surface area, high porosity, high stability, simple preparation, pH response, and good biocompatibility. These attributes make it an ideal carrier is an ideal material for pesticide. This article summarizes the main synthesis methods and commonly used drug-loading strategies of ZIF-8, and focuses on the research progress of ZIF-8 in pesticide loading. The existing issues and future research directions of ZIF-8 as a pesticide carrier were also analyzed, aiming to provide a reference for the research and application of ZIF-8 in the field of pesticide loading. [ABSTRACT FROM AUTHOR]

The purpose of this work is to establish the influence of the nature of solid alginate gels (alginic acid, AAG; calcium alginate, CAG) and the conditions of methylene blue (MB) introduction to alginate matrices upon its release into aqueous media. MB is an active photosensitizer, which is used in the photodynamic therapy of tumors and purulent wounds. Solid alginate gels based on AAG and CAG were obtained by adding hydrochloric acid and calcium chloride to sodium alginate. The dye was introduced into the matrix either at the stage of gelation or by immersing the gel in an aqueous solution of the dye. It has been shown that the strength of the dye's attachment to AAG is higher than that of CAG, which leads to a higher rate of MB release from CAG into aqueous media. It has also been shown that, when introduced at the stage of gel formation, MB is released into both the water and buffer solutions. When MB is introduced by gel immersion into an MB solution, the dye may be released only into salt solutions. An alginate gel with immobilized MB can be used as a solid photosensitizing system with the controlled release of the photoactive agent into the wound cavity for photodynamic treatment. [ABSTRACT FROM AUTHOR]

Diallyl thiosulfinate (DT), a major organosulfur chemical with several notable therapeutic characteristics, is highly unstable and easily degradable which restricts its extensive use in biopharmaceutical commodities. Therefore, utilizing the self-assembly nature of polyoxyethylene (Brij S20 and Brij 58), appropriate pH-responsive micelle carrier systems have been designed to entrap and improve DT's stability at an ambient temperature (25 °C) while preserving its quantity and biological activity. Comparing with the Brij S20 with the Brij 58 micelle carrier system, the latter demonstrated superior stability and entrapment of DT. In addition, it was found that DT's stability in micellized condition is significantly influenced by both pH and temperature (p < 0.05). The micelle system was capable enough to reduce degradation significantly. Additionally, the liberation of DT from micelle is greatly aided by acidic pH 1.5. Around 77% DT was released from Brij 58 system. Various biochemical analyses were done. The liberation of DT from the micelle in a controlled manner using lower pH as stimuli may facilitate its biological action at an individual's gastrointestinal lumen or near cancer cell environment having lower pH. Additionally, it was made sure that the micellization method did not impair DT's bioactivity or reduce appropriate biocompatibility. The current study increases the likelihood of creating a commercially available DT-loaded, micelle-based formulation for application in biopharma and food-related industries. [ABSTRACT FROM AUTHOR]

Bacteriophages have attracted great attention in the bioengineering field in diverse research areas from tissue engineering to therapeutic and clinical applications. Recombinant filamentous bacteriophage, carrying multiple copies of foreign peptides on protein capsid has been successfully used in the vaccine delivery setting, even if their plasma instability and degradation have limited their use on the pharmaceutical market. Encapsulation techniques in polymeric materials can be applied to preserve bacteriophage activity, extend its half-life, and finely regulate their release in the target environment. The main goal of this study was to provide tunable formulations of the bacteriophage encapsulated in polymeric microparticles (MPs). We used poly (lactic-co-glycolic-acid) as a biocompatible and biodegradable polymer with ammonium bicarbonate as a porogen to encapsulate bacteriophage expressing OVA (257–264) antigenic peptide. We demonstrate that nano-engineered fdOVA bacteriophages encapsulated in MPs preserve their structure and are immunologically active, inducing a strong immune response towards the delivered peptide. Moreover, MP encapsulation prolongs bacteriophage stability over time also at room temperature. Additionally, in this study, we show the ability of in silico-supported approach to predict and tune the release of bacteriophages. These results lay the framework for a versatile bacteriophage-based vaccine delivery system that could successfully generate robust immune responses in a sustained manner, to be used as a platform against cancer and new emerging diseases. Synopsis: administration of recombinant bacteriophage-loaded PLGA microparticles for antigen delivery. PLGA microparticles release the bacteriophages, inducing activation of dendritic cells and enhancing antigen presentation and specific T cell response. Bacteriophage-encapsulated microneedles potentially can be administered into human body and generate robust immune responses. [ABSTRACT FROM AUTHOR]

A novel hybrid of a quercetin-loaded silica-chitosan, modified by crosslinked gelatin-folate was developed in the current study as a pH-sensitive drug delivery system. The entrapment efficiency of quercetin was measured at about 77%. The drug release pattern was investigated in acidic and natural media (pH 5.6 and pH = 7.4) for 96 h. In-vitro drug release from unmodified carriers exhibited a rapid release in the early times (57 and 39% after 24 h in acidic and neutral media), which was followed by a slower release. However, the release behavior was improved after modifying the carrier with a gelatin-folate layer. In addition, a further release rate was observed for the gelatin-modified carrier in an acidic medium (31% after 24 h) compared to a neutral condition (20% after 24 h), confirming pH-sensitive behavior. Furthermore, the cumulative release of quercetin from the crosslinked gelatin-folate modified silica-chitosan carrier followed an approximately slow release, so that 23% and 15% of the drug was released after 24 h in acidic and natural conditions, respectively. The release date was described by the Higuchi model, suggesting that both diffusion and polymer swelling control the release process. The high drug loading, pH-triggered behavior, and controlled release of the developed hybrid drug platform, combined with low toxicity, render this designed carrier applicable in targeted drug delivery. [ABSTRACT FROM AUTHOR]

Scaffold‐based tissue engineering provides an efficient approach for repairing uterine tissue defects and restoring fertility. In the current study, a novel trilayer tissue engineering scaffold with high similarity to the uterine tissue in structure was designed and fabricated via 4D printing, electrospinning and 3D bioprinting for uterine regeneration. Highly stretchable poly(l‐lactide‐co‐trimethylene carbonate) (PLLA‐co‐TMC, "PTMC" in short)/thermoplastic polyurethane (TPU) polymer blend scaffolds were firstly made via 4D printing. To improve the biocompatibility, porous poly(lactic acid‐co‐glycolic acid) (PLGA)/gelatin methacryloyl (GelMA) fibers incorporated with polydopamine (PDA) particles were produced on PTMC/TPU scaffolds via electrospinning. Importantly, estradiol (E2) was encapsulated in PDA particles. The bilayer scaffolds thus produced could provide controlled and sustained release of E2. Subsequently, bone marrow derived mesenchymal stem cells (BMSCs) were mixed with gelatin methacryloyl (GelMA)‐based inks and the formulated bioinks were used to fabricate a cell‐laden hydrogel layer on the bilayer scaffolds via 3D bioprinting, forming ultimately biomimicking trilayer scaffolds for uterine tissue regeneration. The trilayer tissue engineering scaffolds thus formed exhibited a shape morphing ability by transforming from the planar shape to tubular structures when immersed in the culture medium at 37°C. The trilayer tissue engineering scaffolds under development would provide new insights for uterine tissue regeneration. [ABSTRACT FROM AUTHOR]

BACKGROUND: Although microencapsulation technology is an effective pesticide formulation method, the correlation between the release properties of microcapsules and pesticide concentrations in soil and their efficacy has not been thoroughly investigated. Here, the effects of the release properties of the nematicide Fosthiazate (FTZ) from microcapsules on their efficacy against the nematode Meloidogyne incognita were examined using experimental and mathematical approaches. RESULTS: Gradual release of FTZ from both polyurea microcapsules (PU‐MC) and melamine‐formaldehyde microcapsules (MF‐MC) was observed over 30 days in the release test, and each release curve was completely distinct. In the biological test, the efficacy of both microcapsules against M. incognita 42 days after the application was 8–15% higher than that of the non‐encapsulated FTZ at a concentration of 2.0 mg FTZ kg−1 soil. Soil degradation experiments suggested that the microcapsules worked effectively to protect the FTZ from degradation, which resulted in higher efficacy at a later stage. A simulation study to predict the concentration of FTZ outside the microcapsule found that the timing of supplying FTZ was important and suggested that the mixture of non‐encapsulated FTZ (non‐MC) and MF‐MC showed enhanced efficiency for the entire cultivation period in the biological test; the efficacy against nematodes was also confirmed by the measurement of nematode density using the Bearman funnel method. CONCLUSION: The release properties of FTZ from microcapsules are critical for their effective application against M. incognita, and the established simulation study is a useful step in designing suitable release properties under complex soil conditions. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Aim: We synthesized MgO NPs via sol-gel reaction and investigated them as carriers to deliver Mg2+ to the affected joint for osteoarthritis (OA). Materials & methods: The physicochemical properties of samples were characterized by transmission electron microscope (TEM), dynamic light scattering (DLS) and x-ray diffraction (XRD). The release of Mg2+ was monitored by ICP-MS. The potential cytotoxicity was evaluated using MTT assay. The efficacy and biosafety were evaluated in a rabbit OA model. Results: MgO NPs can prolong the Mg2+ release time from 0.5 h to 12 h. No significant cytotoxicity was observed when concentrations below 250 μg/ml. Intra-articular samples could effectively alleviate the degeneration and destruction of the cartilage. Conclusion: this study demonstrates the potential of MgO NPs as a safe and effective treatment of OA. Simultaneously, the size of the particles may play a significant role in influencing the therapeutic outcome. Graphical Abstract Article highlights Magnesium oxide nanoparticles (MgO NPs) as the Mg2+ carrier for treatment OA, which not only increases the loading efficiency of Mg2+ but also regulates Mg2+ sustained release. Our investigation not only substantiates the efficacy of MgO NPs in assuaging the pathological manifestations of OA and safeguarding against articular cartilage degradation but also elucidates the correlation between this anti-OA effect and the particle dimensions of MgO NPs per se. Our study not only reinforces the pivotal role of Mg2+ in OA treatment but also underscores the potential of nanoscale strategies in bolstering Mg's therapeutic efficacy. This research lays the foundational groundwork indispensable for the clinical translation of Mg2+ and MgO NPs. [ABSTRACT FROM AUTHOR]

Development of drug delivery systems is an extensively researched area in the biomedical field. In recent years, there has been an increasing interest in fabrication of biocompatible nanofibrous drug delivery systems. The present study describes the fabrication of calcium chloride‐crosslinked bionanocomposite hydrogels based on pectin for the use of gastro‐retentive delivery system. Sepiolite/famotidine/pectin nanocomposite hydrogel was fabricated by using Ionotropic gelation process. The thermal, structural and morphological properties were evaluated via different experimental techniques such as TGA‐DSC, FTIR, and SEM. The prepared hydrogels showed a pH sensitive swelling profile with maximum water absorption at pH 1.2. Analysis of in‐vitro drug release data revealed that the sepiolite/famotidine/pectin nanocomposite hydrogels exhibited a slight initial burst release, followed by a sustained release over a 24 h period. This was observed both in simulated gastric fluid and in phosphate‐buffered saline, suggesting that these hydrogels are well‐suited for prolonged drug delivery. To investigate the drug release kinetics, various models were applied. The release of famotidine was predominantly governed by diffusion, as described by the Korsmeyer‐Peppas model. [ABSTRACT FROM AUTHOR]

BACKGROUND RESULTS CONCLUSION Stimuli‐responsive emulsions have garnered significant attention for their ability to enhance sensory qualities and control the release of encapsulated nutrient in emulsion‐based products. However, the characteristics of synthetic materials of fabricating stimuli‐responsive emulsions have been a crucial limitation in the food industry. Regulating the behavior of molecules at the interface could potentially achieve the desired stimuli‐responsive behavior, but currently there is limited information available.High‐internal‐phase emulsions (HIPEs) were fabricated for the encapsulation of allicin, stabilized by a complex of 20 g kg−1 whey protein amyloid fibrils (WPF) and 20 g kg−1 glycyrrhizin fibers (GA). The intermolecular interactions between WPF and GA in the fiber complexes were predominantly governed by hydrophobic and electrostatic forces. These complexes adsorbed and stacked around the oil droplets, forming a protective interfacial film that enhanced droplet stability. An increased proportion of WPF (WPF = 3:1 or 4:1) surrounding the oil droplets enhanced the accelerated storage stability of HIPEs, with instability indexes approaching 0.2. Additionally, HIPEs displayed a temperature‐dependent modulus, with the emulsion stabilized by a WPF ratio of 3:1 showing the highest modulus at 85 °C. The encapsulation efficiency of allicin in HIPEs ranged from 88.69 ± 6.62% to 101 ± 1.37% at 25 °C, and from 31.95 ± 1.92% to 78.69 ± 4.63% after incubation at 85 °C for 8 h. The release profile of allicin from the HIPEs exhibited thermal responsiveness, depending on the interfacial content of GA.These findings indicated that the thermal‐responsive properties of HIPEs can be strategically engineered by manipulating their interfacial characteristics. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

This article provides insights into hydrogels of the most promising biodegradable natural polymers and their mechanisms of degradation, highlighting the different possibilities of controlling hydrogel degradation rates. Since biodegradable hydrogels can be designed as scaffolding materials to mimic the physical and biochemical properties of natural tissues, these hydrogels have found widespread application in the field of tissue engineering and controlled release. In the same manner, their potential as water reservoirs, macro- and microelement carriers, or matrixes for the selective adsorption of pollutants make them excellent candidates for sustainable soil amendment solutions. Accordingly, this article summarizes the recent advances in natural biodegradable hydrogels in the fields of tissue engineering, controlled release, and soil remediation, emphasizing the new opportunities that degradability and its tunability offer for the design and applicability of hydrogels. [ABSTRACT FROM AUTHOR]

Xanthan gum (XG) is an exopolysaccharide synthesized by the aerobic fermentation of simple sugars using Xanthomonas bacteria. It comprises a cellulosic backbone with a trisaccharide side chain connected to alternative glucose residues in the main backbone through α (1→3) linkage. XG dissolves readily in cold and hot water to produce a viscous solution that behaves like a pseudoplastic fluid. It shows excellent resistance to enzymatic degradation and great stability throughout a broad temperature, pH, or salt concentration range. Additionally, XG is nontoxic, biocompatible, and biodegradable, making it a suitable carrier for drug delivery. Furthermore, the carboxylic functions of pyruvate and glucuronic acid offer a considerable opportunity for chemical modification to meet the desired criteria for a specific application. Therefore, XG or its derivatives in conjunction with other polymers have frequently been studied as matrices for tablets, nanoparticles, microparticles, and hydrogels. This review primarily focuses on the applications of XG in various oral delivery systems over the past decade, including sustained-release formulations, gastroretentive dosage forms, and colon-targeted drug delivery. Source, production methods, and physicochemical properties relevant to drug delivery applications of XG have also been discussed. [ABSTRACT FROM AUTHOR]

Summary This article aimed at reviewing recent developments shaping the future of antimicrobial edible food packaging. The main issues discussed in the article are (i) factors (e.g. waste valorisation, sustainability, health and environmental concerns, religious concerns, etc.) causing emerging of alternative hydrocolloids extracted from farming/processing wastes of plants, animals, fungi, insects, snails, etc. as antimicrobial edible packaging material; (ii) emerging methods of manufacturing antimicrobial packaging (e.g. extruded and co‐extruded antimicrobial casings, antimicrobial electrospun mats, and electrosprayed films, coatings and particles); (iii) emerging concepts in using natural antimicrobials in edible packaging such as using narrow‐ or broad‐spectrum antimicrobials, synergetic mixtures, and controlled release strategies based on nanoencapsulation (e.g. Pickering emulsions, nanoemulsions, inclusion complexes, solid lipid nanoparticles and nanostructured lipid carriers). This review helps discovering the future of active edible packaging that is expected to play a central role in improving food safety and quality, human health and environmentally friendly practices. [ABSTRACT FROM AUTHOR]

A common challenge in hydrogel-based delivery systems is the premature release of low molecular weight encapsulates through diffusion or swelling and reduced cell viability caused by the low pH in gastric conditions. A second biopolymer, such as chitosan, can be incorporated to overcome this. Chitosan is usually associated with colonic drug delivery systems. We intended to formulate chitosan-coated pectin beads for use in delaying premature release of the encapsulate under gastric conditions but allowing release through disintegration under intestinal conditions. The latter is of utmost importance in delivering most functional food ingredients. Therefore, this study investigated the impact of formulation and process conditions on the size, sphericity, and dissolution behavior of chitosan-coated hydrogel beads prepared by interfacial coacervation. The size and sphericity of the beads depend on the formulation and range from approximately 3 to 5 mm and 0.82 to 0.95, respectively. Process conditions during electro-dripping may be modulated to tailor bead size. Depending on the voltage, bead size ranged from 1.5 to 4 mm. Confocal laser scanning microscopy and scanning electron microscopy confirmed chitosan shell formation around the pectin bead. Chitosan-coated beads maintained their size and shape in simulated gastric fluid but experienced structural damage in simulated intestinal fluid. Therefore, they represent a novel delivery system for functional food ingredients. [ABSTRACT FROM AUTHOR]

Layered double hydroxides (LDHs) are biocompatible materials with excellent anion exchange properties, making them suitable for use as drug carriers by incorporating the drug in its anionic form within their layered structure. In this study, an LDH was synthetized through ion exchange with valproate (VAL), an anticonvulsant drug, using an LDH with nitrate as the parent material. The resulting LDH-VAL sample underwent a comprehensive multi-technique characterization using XRD, TG-DSC, TEM, SEM, EDS, FTIR, XPS and zeta potential measurements. Dissolution kinetics and VAL release kinetics in an ample range of pH (3–9), along with biological assays to test biocompatibility, were also performed. All techniques confirmed the successful intercalation of the drug into the LDH structure, displacing all the nitrate ions of the parent material and increasing the basal spacing d 003 from 8.8 Å to 18.3 Å. VAL release in NaCl and physiological buffer solutions was incongruent with LDH dissolution, clearly indicating that VAL release was controlled by an ion exchange process. In 0.9 % NaCl solutions, 90–100 % of VAL was released with only 15–20 % of LDH dissolution, and in buffer solutions 100 % of VAL was released with, at the most, 30 % of LDH dissolution. Biological assays, including lactate dehydrogenase activity, serum calcium concentration and histological analysis of blood samples, confirmed that the prepared LDH-VAL is a biocompatible material with a potential use as a nanodrug carrier. [Display omitted] [ABSTRACT FROM AUTHOR]

Some degree of localized hypoxia can cause varying degrees of cellular damage in tissues. Oxygen-releasing biomaterials can sustainably provide oxygen to transplanted cells. In recent years, extensive research efforts have been dedicated to developing more pratical oxygen-releasing biomaterials and systems to enhance oxygen delivery in vivo and ensure effective oxygen supply to implanted tissues. Based on the form of oxygen provision, these materials can be calssified into oxygen-carrying materials and oxygen-producing materials. The former deliver therapeutic oxygenation by binding oxygen molecules under specific conditions, while the latter incorporate oxygen source materials into polymers, achieving oxygen release through in vivo hydrolysis. This paper summarizes the current development of oxygen-carrying materials and oxygen-producing materials, including oxygen source supply, loading materials, and controlled release. It discusses practical application of oxygen-releasing biomaterials for oxygen delivery and various strategies for controlled release. [ABSTRACT FROM AUTHOR]

Purpose: The present study aimed to determine the dose–response relationship between targeted nanocarriers released from a novel, sustained release formulation and their ability to specifically deplete cells responsible for the development of posterior capsular opacification (PCO) in month-long, dynamic cell cultures. Methods: Injectable, thermosensitive poly(D,L-lactic-co-glycolic acid)-b-poly(ethylene glycol)-b-poly(D,L-lactic-co-glycolic acid) triblock copolymer hydrogels were loaded with either a low or a high dose of doxorubicin-loaded antibody-targeted nanocarriers (G8:3DNA:Dox). Human rhabdomyosarcoma cells, selected for their expression of PCO marker brain-specific angiogenesis inhibitor 1 (BAI1), were kept under dynamic media flow and received either a low or high dose of nanocarriers. Cells were fixed and stained at predetermined time points to evaluate targeted depletion of BAI1+ cells. Results: A lower dose of nanocarriers in hydrogel depleted BAI1+ cells at a slower rate than the higher dose, whereas both reached over 90% BAI1+ cellular nonviability at 28 days. Both treatment groups also significantly lowered the relative abundance of BAI1+ cells in the population compared with the control group. Conclusions: Controlled release of a lower dose of nanocarriers can still achieve therapeutically relevant effects in the prevention of PCO, while avoiding potential secondary effects associated with the administration of a higher dose. [ABSTRACT FROM AUTHOR]

Simple Summary: Pancreatic cancer is one of the most deadly forms of cancer. Current treatment options often fail because too little of the chemotherapy gets into the cancer. Hyperthermia, or heat treatment, has shown some promise in treating pancreatic cancer and may make it more likely for the chemotherapy to enter into the cancer. This study aims to design liposomes that can increase the amount of chemotherapy reaching pancreatic cancer by targeting the liposomes with hyperthermia. Treatment of pancreatic ductal adenocarcinoma with gemcitabine is limited by an increased desmoplasia, poor vascularization, and short plasma half-life. Heat-sensitive liposomes modified by polyethylene glycol (PEG; PEGylated liposomes) can increase plasma stability, reduce clearance, and decrease side effects. Nevertheless, translation of heat-sensitive liposomes to the clinic has been hindered by the low loading efficiency of gemcitabine and by the difficulty of inducing hyperthermia in vivo. This study was designed to investigate the effect of phospholipid content on the stability of liposomes at 37 °C and their release under hyperthermia conditions; this was accomplished by employing a two-stage heating approach. First the liposomes were heated at a fast rate, then they were transferred to a holding bath. Thermosensitive liposomes formulated with DPPC: DSPC: PEG2k (80:15:5, mole%) exhibited minimal release of carboxyfluorescein at 37 °C over 30 min, indicating stability under physiological conditions. However, upon exposure to hyperthermic conditions (43 °C and 45 °C), these liposomes demonstrated a rapid and significant release of their encapsulated content. The encapsulation efficiency for gemcitabine was calculated at 16.9%. Additionally, fluorescent analysis during the removal of unencapsulated gemcitabine revealed an increase in pH. In vitro tests with BxPC3 and KPC cell models showed that these thermosensitive liposomes induced a heat-dependent cytotoxic effect comparable to free gemcitabine at temperatures above 41 °C. This study highlights the effectiveness of the heating mechanism and cell models in understanding the current challenges in developing gemcitabine-loaded heat-sensitive liposomes. [ABSTRACT FROM AUTHOR]

When a new molecular entity is predicted to exhibit high clearance in humans, pharmaceutical sponsors almost universally search for similar acting back-up compounds that will demonstrate low clearance. Here we show that, except for oral dosing, there can be marked advantages to developing and commercializing controlled release formulations of high clearance drugs, the expertise of readers of this journal. Our recent publications demonstrate that the universally held pharmacokinetic principle that drug delivery rate has no effect on measured drug clearance is not correct. Rather, we show that if clearance from the drug delivery site is markedly less than the iv bolus clearance of a drug, the in vivo drug clearance can be the drug delivery clearance controlled by the designed dosage form. This approach will be especially advantageous for high hepatic clearance drugs. These advantages include not being concerned with: a) saturable nonlinear kinetics, b) significant pharmacogenomic differences, c) drug-drug induction mechanisms, and d) in many cases drug-drug inhibition interactions. This is due to the ability of a drug sponsor to design clearance, independent of the pharmacokinetic characteristics for high clearance compounds, where clearance from the dosage form becomes the drug clearance from the patient. Recognition of this principle, as described here, results from our development of the use of Kirchhoff's Laws from physics to derive rate-defining clearance and rate constant elimination processes independent of differential equation derivations. The key message for readers of this journal is that high clearance drugs are potentially drugable through formulation design and should not be outright disregarded, since for such drugs the dose-corrected area under the curve can be increased if the release rate from the injection site is controlled and slow resulting in drug clearance from the body controlled by clearance from the dosage form. The concepts presented here describe previously unrecognized advantages of controlled release formulations. [Display omitted] [ABSTRACT FROM AUTHOR]

Immunosuppressive tumor-associated macrophages (TAMs) account for a high proportion of the tumor tissue and significantly impede immunoefficacy. Furthermore, the signal regulatory protein α (SIRPα) expressed in TAMs adversely correlates with macrophage activation and phagocytosis, resulting in immunosurveillance escape. To address these difficulties, a mannose-modified, pH-responsive nanoplatform with resiquimod (R848) and 2′, 3′-cyclic GMP-AMP (cGAMP) co-encapsulation (named M-PNP@R@C) is designed to polarize TAMs and lower SIRPα expression. The co-delivery of R848 and cGAMP synergistically facilitates the polarization of TAMs from the anti-inflammatory M2 phenotype into the pro-inflammatory M1 phenotype, thereby enhancing antitumor immunotherapy. Remarkably, activation of the cGAMP-mediated stimulator of interferon genes (STING) in TAMs significantly downregulates the expression of SIRPα, which synergizes with the cluster of differentiation 47 (CD47) antibody for the dual blockade of the CD47-SIRPα axis. Further analysis of single-cell RNA sequencing indicates that STING activation downregulates SIRPα by regulating intracellular fatty acid oxidation metabolism. In vivo studies indicate that M-PNP@R@C significantly inhibits tumor growth with a potent antitumor immune response in melanoma graft tumor models. After synergy with anti-CD47, the double blockade strategies of the SIRPα/CD47 axis result in a notable inhibition of lung metastasis. A prolonged survival rate is observed after combination treatment with CD47 and programmed death ligand-1 antibodies for the triple immune checkpoint blockade. In summary, our study provides original insights into the potential role of the STING pathway in macrophage-based immunotherapy, thus offering a potential combinatorial strategy for cancer therapy. [Display omitted] • M-PNP@R@C induces TAMs polarization due to the dual effects of R848 and cGAMP. • STING activation in TAMs downregulates SIRPα expression via FAO metabolism regulation. • M-PNP@R@C dispalys high antitumor activity due to TAMs polarization and SIRPα downregulation mediated phagocytosis. • The double blockades of SIRPα/CD47 axis after combination with aCD47 inhibit lung metastasis. • The triple immune checkpoint blockades after further combination with aPD-L1 prolong survival rate. [ABSTRACT FROM AUTHOR]

For decades, drug delivery scientists have been performing trial-and-error experimentation to manually sample parameter spaces and optimize release profiles through rational design. To enable this approach, scientists spend much of their career learning nuanced drug-material interactions that drive system behavior. In relatively simple systems, rational design criteria allow us to fine tune release profiles and enable efficacious therapies. However, as materials and drugs become increasingly sophisticated and their interactions have non-linear and compounding effects, the field is suffering the Curse of Dimensionality which prevents us from comprehending complex structure-function relationships. In the past, we have embraced this complexity by implementing high-throughput screens to increase the probability of finding ideal compositions. However, this brute force method was inefficient and led many to abandon these fishing expeditions. Fortunately, methods in data science including artificial intelligence / machine learning (AI/ML) are providing ideal analytical tools to model this complex data and ascertain quantitative structure-function relationships. In this Oration, I speak to the potential value of data science in drug delivery with particular focus on polymeric delivery systems. Here, I do not suggest that AI/ML will simply replace mechanistic understanding of complex systems. Rather, I propose that AI/ML should be yet another useful tool in the lab to navigate complex parameter spaces. The recent hype around AI/ML is breathtaking and potentially over inflated, but the value of these methods is poised to revolutionize how we perform science. Therefore, I encourage readers to consider adopting these skills and applying data science methods to their own problems. If done successfully, I believe we will all realize a paradigm shift in our approach to drug delivery. [Display omitted] • Complex drug-material interactions challenge the design of drug delivery systems. • Machine learning is useful for navigating large parameter spaces and structure-function modeling. • When coupled with automation, the drug delivery community may see significant gains in productivity. [ABSTRACT FROM AUTHOR]

Meat and meat products are highly susceptible to contamination by microorganisms and foodborne pathogens, which cause serious economic losses and health hazards. The large consumption and waste of meat and meat products means that there is a need for safe and effective preservation methods. Furthermore, toxicological aspects of chemical preservation techniques related to major health problems have sparked controversies and have prompted consumers and producers to turn to natural preservatives. Consequently, natural preservatives are being increasingly used to ensure the safety and quality of meat products as a result of customer preferences and biological efficacy. However, information on the current status of these preservatives is scattered and a comprehensive review is lacking. Here, we review current knowledge on the classification, mechanisms of natural preservatives and their applications in the preservation of meat and meat products, and also discuss the potential of natural preservatives to improve the safety of meat and meat products. The current status and the current research gaps in the extraction, application and controlled‐release of natural antibacterial agents for meat preservation are also discussed in detail. This review may be useful to the development of efficient food preservation techniques in the meat industry. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Nowadays, the use of lipid-based nanocarriers for the targeted and controlled delivery of a variety of hydrophobic and hydrophilic bioactive-compounds and drugs has increased significantly. However, challenges such as thermodynamic instability, oxidation, and degradation of lipid membranes, as well as the unintended release of loaded compounds, have limited the use of these systems in the food and pharmaceutical industries. Therefore, the present study reviews the latest achievements in evaluating the characteristics, production methods, challenges, functional, and biological stabilization strategies of lipid-based carriers (including changes in formulation composition, structural modification, membrane-rigidity, and finally monolayer or multilayer coating with biopolymers) in different conditions, as well as molecular dynamics simulations. The scientists' findings indicate the effect of natural biopolymers (such as chitosan, calcium alginate, pectin, dextran, xanthan, caseins, gelatin, whey-proteins, zein, and etc.) in modifying the external structure of lipid-based carriers, improving thermodynamic stability and resistance of membranes to physicochemical and mechanical tensions. However, depending on the type of bioactive compound as well as the design and production goals of the delivery-system, selecting the appropriate biopolymer has a significant impact on the stability of vesicles and maintaining the bioaccessibility of the loaded-compounds due to the stresses caused by the storage-conditions, formulation, processing and gastrointestinal tract. [ABSTRACT FROM AUTHOR]

Battlefield wounds are at high risk of infection due to gross contamination and delays in evacuation from forward‐deployed locations. The aim of this study was to formulate an antibiotic wound gel for application by a field medic in austere environments to protect traumatic wounds from infection during transport. Formulation development was conducted over multiple phases to meet temperature, handling, in vitro elution, and in vivo tissue response requirements. Thermal properties were evaluated by vial inversion, DSC, and syringe expression force in a temperature range of 4–49°C. Handling was evaluated by spreading onto blood‐contaminated tissue and irrigation resistance. Controlled antibiotic release was evaluated by a modified USP immersion cell dissolution method. Local tissue effects were evaluated in vivo by subcutaneous implantation in rats for 7 and 28 days. An oleogel composition of cholesterol, hydrogenated castor oil, soybean oil, and glyceryl monocaprylocaprate met the target performance criteria. Peak expression force from a 5 mL syringe at 4°C was 48.3 N, the dropping point temperature was 68°C, and the oleogel formulation could be spread onto blood‐contaminated tissue and resisted aqueous irrigation. The formulation demonstrated sustained release of tobramycin in PBS at 32°C for 5 days. Implantation in a rat dorsal pocket demonstrated a slight tissue reaction after 7 days with minimal to no reaction after 28 days, comparable to a commercial hemostat control. Material resorption was evident after 28 days. The formulation met target characteristics and is appropriate for further evaluation in a large animal contaminated blast wound model. [ABSTRACT FROM AUTHOR]

Vegetable-oil-based polyurethane has become a promising sustainable candidate for controlled-release fertilizer based on green chemistry. The purpose of this study was to prepare a series of coatings from selective feedstocks including five vegetable oils with a high saturation degree, mono-unsaturation degree, or poly-unsaturation degree, considering that vegetable oil fatty acids played a key role in the synthesis of polyol and polyurethane. The effect of the type and proportion of fatty acids on the physicochemical properties, microstructure, and macro-properties of vegetable-oil-derived polyols and their resulting coatings was characterized and discussed. The position and number of the hydroxy groups were determined by the type and proportion of fatty acid, and polyol from linseed oil with a high poly-unsaturation degree and three carbon–carbon double bonds had a high hydroxyl value and functionality, whereas polyol from palm oil with a high saturation degree possessed the lowest hydroxyl value and functionality. The resultant coating from linseed-oil-based polyol had a good cross-linking density, and the nitrogen release longevity of coated urea was 56 days at a coating percentage of 3%, and its nitrogen use efficiency was increased by 27.15% compared with conventional urea. Although the palm-oil-based coating had good hydrophobicity, its coated urea was not ideal. Overall, this study has enriched theories of bio-based polyurethane coatings for controlled-release fertilizers; using vegetable oil with a poly-unsaturation degree, it is easy to obtain an excellent coating for controlled-release fertilizer, and this will help provide economic and environmental benefits. [ABSTRACT FROM AUTHOR]

Controlled-release fertilisers are granular particles coated with a polymer that can release nutrients over a long time by preventing moisture contact and allowing the fertiliser to dissolve gradually. Stimuli-responsive controlled-release fertilisers also called smart fertilisers allow for passive nutrient release through response of environmental stimuli. External stimuli may be pH, temperature, redox conditions, enzymes, and light. The respiration from the roots of plants increases the amount of CO2 in the rhizosphere that decreases the pH in the soil. The properties of polymer-coated fertilisers change because of temperature variation and thereby release the fertiliser. The gel polymers swell as the temperature rises and contract as the temperature decreases. Enzyme-responsive polymers are highly useful in the delivery of insecticides safely exactly to the target. In redox-responsive polymers, the colour, fluorescence ability, and chirality vary according to external redox reactions. Chitosan is made from the outer skeleton of shellfish, crab, lobster, and shrimp. Chitosan possesses antimicrobial activity that finds applications in drug manufacturing. Chitosan can be modified to become chitosan nanoparticles through various synthesis techniques. In addition to its medical applications, chitosan nanoparticles are used in agriculture to encapsulate macronutrients such as nitrogen, phosphorus, and potassium (NPK). NPK fertilisers are essential for the growth of plants. These three essential nutrients are loaded into chitosan nanoparticles. Nanofertilisers are macro- or micronutrients that are encapsulated within nanomaterials so that they can be released slowly or in a controlled manner and allow a slow diffusion into the soil. Commercialisation of nanofertilisers for use in agriculture will support farmers. An increased uptake of nutrients by crops, low fertiliser utilisation, more yield, prevention of over-fertilisation, and reducing the wastage of fertilisers are achieved. Farmers can adopt this new advanced technology in their farming by easily accessing these nano-fertiliser products. [ABSTRACT FROM AUTHOR]

Fluorouracil (5-FU) has been the most widely used chemotherapy agent since its clinical introduction in 1957, and it continues to form the basis of treatment for various cancers. However, due to the side effects of an antimetabolite, a strategy fulfilling stringent requirements placed on a 5-FU delivery system requires controlled and extended release of 5-FU in a localized manner. Here, an in-situ gel-forming method for the preparation of micropatterned, α-chymotrypsin-degradable hydrogel (PHcd) for controlled release of 5-FU is introduced. More specifically, methacrylated hyaluronic acid (HA) and polyethylene glycol diacrylate (PEGDA), known for their excellent moisture retention capacity, are chosen for skin therapy. They are crosslinked with CYKC peptide through a thiol-ene click reaction. The synthesis of the CYKC peptide and its cleavage by α-chymotrypsin were confirmed using high-performance liquid chromatography (HPLC). Additionally, the in vitro release behavior was accurately monitored using the micropatterning method, demonstrating the stable immobilization and successful sustained release of 5-FU upon the addition of α-chymotrypsin in micropatterned PHcd hydrogel. Consequently, this micropatterned PHcd hydrogel can be considered a promising scaffold for localized and sustained delivery of cytotoxic drugs for skin cancer treatment. [ABSTRACT FROM AUTHOR]

[Display omitted] Cartilage is severely limited in self-repair after damage, and tissue engineering scaffold transplantation is considered the most promising strategy for cartilage regeneration. However, scaffolds without cells and growth factors, which can effectively avoid long cell culture times, high risk of infection, and susceptibility to contamination, remain scarce. Hence, we developed a cell- and growth factor-dual free hierarchically structured nanofibrous sponge to mimic the extracellular matrix, in which the encapsulated core–shell nanofibers served both as mechanical supports and as long-lasting carriers for bioactive biomass molecules (glucosamine sulfate). Under the protection of the nanofibers in this designed sponge, glucosamine sulfate could be released continuously for at least 30 days, which significantly accelerated the repair of cartilage tissue in a rat cartilage defect model. Moreover, the nanofibrous sponge based on carboxymethyl chitosan as the framework could effectively fill irregular cartilage defects, adapt to the dynamic changes during cartilage movement, and maintain almost 100 % elasticity even after multiple compression cycles. This strategy, which combines fiber freeze-shaping technology with a controlled-release method for encapsulating bioactivity, allows for the assembly of porous bionic scaffolds with hierarchical nanofiber structure, providing a novel and safe approach to tissue repair. [ABSTRACT FROM AUTHOR]

Antimicrobial or antioxidant active packaging (AP) is an emerging technology in which a bioactive antimicrobial or antioxidant agent is incorporated into the packaging material to protect the contained product during its shelf life from deterioration. The important issue in AP is making a balance between the deterioration rate of the food product and the controlled release of the bioactive agent. So, the AP fabrication should be designed in such a way that fulfills this goal. Modeling the controlled release is an effective way to avoid trial and error and time-consuming experimental runs and predict the release behavior of bioactive agents in different polymeric matrices and food/food simulants. To review the release of bioactive compounds from AP, in the first part of this review we present an introductory explanation regarding the release controlling approaches in AP. Then the release mechanisms are explained which are very important in defining the appropriate modeling approach and also the interpretation of the modeling results. Different release profiles that might be observed in different packaging systems are also introduced. Finally, different modeling approaches including empirical and mechanistic techniques are covered and the recent literature regarding the utilization of such approaches to help design new AP is thoroughly studied. [ABSTRACT FROM AUTHOR]