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This study proposes the application of carboxymethyl starch derivatives as tablet coatings affording gastro-protection. Carboxymethyl starch (CMS) films were obtained by casting of aqueous filmogenic starch solutions with or without plasticizers and their structural organization was followed using Fourier transform infrared (FTIR), Thermogravimetric analysis (TGA), X-ray diffraction (XRD). Together with data from mechanical tests (tensile strength, elongation, Young's modulus) the results were used to select filmogenic formulations adapted for coatings of tablets. The behaviour of these films was evaluated in simulated gastric and intestinal fluids. The effect of plasticizers (glycerol and sorbitol) on the starch organization, on the rate of drying of the films and on the water vapor absorption was also analyzed. Various types of starch have been compared and the best results were found with high amylose starch (HAS) that was carboxymethylated in an aqueous phase to obtain carboxymethyl high amylose starch (CMHAS). The CMHAS coating solutions containing sorbitol or glycerol as plasticizers have been applied with an industrial pan coater and the final tablets exhibited a good gastro-resistance (up to 2h) in simulated gastric fluid followed by disintegration in simulated intestinal fluid (SIF). The CMHAS derivatives present a high potential as coatings for nutraceutical and pharmaceutical solid dosage forms. [Display omitted] • Homogeneous coatings were obtained using an aqueous formulation of CMHAS and sorbitol plasticizer. • CMHAS enteric coatings resisted for 2h in gastric acidity (pH 1.2) and were disrupted only at neutral pH 6.8. • Reduced solubility and high mechanical strength of CMHAS cast films are predictive for the selection of a good enteric coating formulation. • In the presence of alpha-amylase at neutral pH the coatings were totally disintegrated. • Amylose: Amylopectin ratio and gelatinization conditions are determinants for the CMHAS coating features. [ABSTRACT FROM AUTHOR]

Hydroxypropyl methylcellulose (HPMC) is a preferred hydrophilic matrix former for controlled release formulations produced through continuous twin-screw wet granulation. However, a non-homogeneous API distribution over sieve fractions with underdosing in the fines fraction (<150 µm) was previously reported. This could result in content uniformity issues during downstream processing. Therefore, the current study investigated the root cause of the non-homogeneous theophylline distribution. The effect of process parameters (L/S-ratio and screw configuration) and formulation parameters (matrix former and filler type) on content uniformity was studied. Next, the influence of the formulation parameters on tableting and dissolution behavior was investigated. Altering the L/S-ratio or using a more aggressive screw configuration did not result in a homogeneous API distribution over the granule sieve fractions. Using microcrystalline cellulose (MCC) as filler improved the API distribution due to its similar behavior as HPMC. As excluding HPMC or including a hydrophobic matrix former (Kollidon SR) yielded granules with a homogeneous API distribution, HPMC was identified as the root cause of the non-homogeneous API distribution. This was linked to its fast hydration and swelling (irrespective of the HPMC grade) upon addition of the granulation liquid. [ABSTRACT FROM AUTHOR]

Due to the unstable chemical properties and poor water solubility of carotenoids, their processing adaptation and oral bioavailability are poor, limiting their application in hydrophilic food systems. Lipid-biomacromolecular compounds can be excellent carriers for carotenoid delivery by taking full advantage of the solubilization of lipids to non-polar nutrients and the water dispersion and gastrointestinal controlled release properties of biomacromolecules. This paper reviewed the research progress of lipid-biomacromolecular compounds as encapsulation and delivery carriers of carotenoids and summarized the material selection and preparation methods for biomacromolecular compounds. By considering the interaction between the two, this paper briefly discussed the effect of these compounds on carotenoid water solubility, stability, and bioavailability, emphasizing their delivery effect on carotenoids. Finally, various challenges and future trends of lipid-biomacromolecular compounds as carotenoid delivery carriers were discussed, providing new insight into efficient loading and delivery of carotenoids. [ABSTRACT FROM AUTHOR]

Waterglass-calcium chloride compound is a commonly used lost circulation material. When use this material to control mud losses, the waterglass reacts instantly with calcium chloride as soon as the two chemicals are brought together. Thus, mud loss control with waterglass-calcium chloride compound can only be performed in a complicated “two-liquids” method. To make things easy, the release of calcium chloride from the compound lost circulation material is controlled to try to pump the mixture of waterglass and calcium chloride in one operation. In this study, a resin is used to wrap calcium chloride for controlled release of calcium chloride. By changing the quantities of calcium chloride and the crosslinking agent as well as the type and ratio of the monomers, the effects of these factors on the release of calcium chloride can be understood. The study shows that when wrapping calcium chloride with the resin, if the mass ratio of calcium chloride and the monomer is 1∶4 and the concentration of the crosslinking is 6%, then the time for the waterglass-calcium chloride system to lose fluidity can be extended to 105 min. When the powdered resin wrapping up calcium chloride is rewrapped, if the mass ratio of calcium chloride and the monomer is 1∶2, and the concentrations of the crosslinking agent are both 6% in the first and secondary wrapping, the time for the waterglass-calcium chloride system to lose fluidity can then be extended to 115 min. If sodium chloride is added in the secondary wrapping, then the time for the system to lose fluidity can be extended to 180 min. Analyses with IR spectrum and SEM show that the water-absorbing resin retards the reaction between calcium chloride and waterglass by reducing the contact area between the two chemicals, while the resin itself does not participate in the reaction between waterglass and calcium chloride [ABSTRACT FROM AUTHOR]

Essential oils have become increasingly popular in fields of medical, food and agriculture, owing to their strongly antimicrobial, anti-inflammation and antioxidant effects, greatly meeting demand from consumers for healthy and safe natural products. However, the easy volatility and/or chemical instability of active ingredients of essential oils (EAIs) can result in the loss of activity before realizing their functions, which have greatly hindered the widely applications of EAIs. As an emerging trend, micro/mesoporous nanomaterials (MNs) have drawn great attention for encapsulation and controlled release of EAIs, owing to their tunable pore structural characteristics. In this review, we briefly discuss the recent advances of MNs that widely used in the controlled release of EAIs, including zeolites, metal-organic frameworks (MOFs), mesoporous silica nanomaterials (MSNs), and provide a comprehensive summary focusing on the pore engineering strategies of MNs that affect their controlled-release or triggered-release for EAIs, including tailorable pore structure properties (e.g. , pore size, pore surface area, pore volume, pore geometry, and framework compositions) and surface properties (surface modification and surface functionalization). Finally, the variegated applications and potential challenges are also given for MNs based delivery strategies for EAIs in the fields of healthcare, food and agriculture. These will provide considerable instructions for the rational design of MNs for controlled release of EAIs. [Display omitted] • Recent advances in MNs for encapsulation and controlled release of EAIs. • Outlook in pore engineering strategies of MNs for controlled release of EAIs. • Perspectives and challenges in variegated applications of MNs for EAIs. [ABSTRACT FROM AUTHOR]

Over the years, infectious diseases have significantly contributed to the mortality and morbidity rates in the healthcare system. Conventional treatments have been used for many years to treat infectious diseases, such as oral and topical drug delivery routes. However, these treatments present numerous challenges. The factors such as the solubility of the drug, its size and its molecular weight may affect the efficacy of conventional therapies. Nanotechnology or nanomedicine is one of the novel and promising approaches to overcome these aforementioned challenges for traditional therapies. Solid lipid nanoparticles are a novel approach in the drug delivery system which was first introduced in early 1990s. Their small size, large surface area, high drug loading and the ability to interact with other phases, solid lipid nanoparticles are attractive for improving the performance of pharmaceutical, nutraceutical and other materials. Solid lipid nanoparticles have been proven to be one of the most effective methods of treating infectious diseases (antibiotic-loaded solid lipid nanoparticles). This review emphasizes solid lipid nanoparticles as a delivery system for infectious diseases. Also, it discusses research pertaining to the targeting approach of solid lipid nanoparticles in infections. [ABSTRACT FROM AUTHOR]

Core–shell structure is a concentric circle structure found in nature. The rapid development of electrospinning technology provides more approaches for the production of core–shell nanofibers. The nanoscale effects and expansive specific surface area of core–shell nanofibers can facilitate the dissolution of drugs. By employing ingenious structural designs and judicious polymer selection, specialized nanofiber drug delivery systems can be prepared to achieve controlled drug release. The synergistic combination of core–shell structure and materials exhibits a strong strategy for enhancing the drug utilization efficiency and customizing the release profile of drugs. Consequently, multi‐chamber core–shell nanofibers hold great promise for highly efficient disease treatment. However, little attention concentration is focused on the effect of multi‐chamber core–shell nanofibers on controlled release of drugs. In this review, we introduced different fabrication techniques for multi‐chamber core–shell nanostructures, including advanced electrospinning technologies and surface functionalization. Subsequently, we reviewed the different controlled drug release behaviors of multi‐chamber core–shell nanofibers and their potential needs for disease treatment. The comprehensive elucidation of controlled release behaviors based on electrospun multi‐chamber core–shell nanostructures could inspire the exploration of novel controlled delivery systems. Furthermore, once these fibers with customizable drug release profiles move toward industrial mass production, they will potentially promote the development of pharmacy and the treatment of various diseases. This article is categorized under:Therapeutic Approaches and Drug Discovery > Emerging Technologies [ABSTRACT FROM AUTHOR]

Remote loading microencapsulation of peptides into polymer microspheres without organic solvent represents a promising alternative to develop long-acting release depots relative to conventional encapsulation methods. Here, we formulated drug-free microspheres from two kinds of uncapped poly(lactide-co-glycolides) (PLGAs), i.e., ring-opening polymerized Expansorb® DLG 50-2A (50/50, 11.2 kDa) and Expansorb® DLG 75-2A (75/25, 9.0 kDa), and evaluated their potential capacity to remote-load and control the release of two model peptides, leuprolide and octreotide. Degradation and erosion kinetics, release mechanism, and storage stability was also assessed. As control formulations, peptide was loaded in the same PLGA 75/25 polymer by the conventional double emulsion-solvent evaporation method (W/O/W) and remote loaded in polycondensation poly(lactic-co-glycolic acid) 75/25 (Wako 7515, 14.3 kDa). Loading content of 6.7%–8.9% w/w (~ 67%–89% encapsulation efficiency (EE)) was attained for octreotide, and that of 9.5% w/w loading (~ 95% EE) was observed for leuprolide, by the remote loading paradigm. Octreotide and leuprolide were both slowly and continuously released in vitro from the remote-loaded Expansorb® DLG 75-2A MPs for over 56 days, which was highly similar to that observed from traditionally-loaded formulations by W/O/W (8.8% loading, 52.8% EE). The faster release kinetics was observed for the faster degrading PLGA 50/50 remote-loaded Expansorb® DLG 50-2A MPs relative to microspheres from the PLGA 75/25 Expansorb® DLG 75-2A. Despite slight differences in degradation kinetics, the release mechanism of octreotide from the Expansorb® microspheres, whether remote loaded or by W/O/W, was identical as determined by release vs. mass loss curves. Octreotide acylation was also minimal (< ~ 10%) for this polymer. Finally, drug-free Expansorb® DLG 75-2A MPs displayed excellent storage stability over 3 months. Overall, this work offers support for the use of ring-opening Expansorb® PLGA-based microspheres to remote load peptides to create simple and effective long-acting release depots. [ABSTRACT FROM AUTHOR]

Background: Pesticide formulations based on nanotechnology can effectively improve the efficiency of pesticide utilization and reduce pesticide residues in the environment. In this study, mesoporous silica nanoparticles containing disulfide bonds were synthesized by the sol–gel method, carboxylated and adsorbed with lufenuron, and grafted with cellulose to obtain a lufenuron‐loaded nano‐controlled release formulation (Luf@MSNs‐ss‐cellulose). Results: The structure and properties of Luf@MSNs‐ss‐cellulose were characterized. The results showed that Luf@MSNs‐ss‐cellulose exhibits a regular spherical shape with 12.41% pesticide loading. The highest cumulative release rate (73.46%) of this pesticide‐loaded nanoparticle was observed at 7 days in the environment of glutathione and cellulase, which shows redox‐enzyme dual‐responsive performance. As a result of cellulose grafting, Luf@MSNs‐ss‐cellulose had a small contact angle and high adhesion work on corn leaves, indicating good wetting and adhesion properties. After 14 days of spraying with 20 mg L−1 formulations in the long‐term control efficacy experiment, the mortality of Luf@MSNs‐ss‐cellulose against Ostrinia furnacalis larvae (56.67%) was significantly higher than that of commercial Luf@EW (36.67%). Luf@MSNs‐ss‐cellulose is safer for earthworms and L02 cells. Conclusion: The nano‐controlled release formulation obtained in this study achieved intelligent pesticide delivery in time and space under the environmental stimulation of glutathione and cellulase, providing an effective method for the development of novel pesticide delivery systems. © 2023 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Precision medicine is the next frontier in pharmaceutical research, aiming to improve the safety and efficacy of therapeutics for patients. The ideal drug delivery system (DDS) should be programmable to provide real-time controlled delivery that is personalised to the patient's needs. However, little progress has been made in this domain. Herein, we combined two cutting-edge technologies, conductive polymers (CPs) and three-dimensional (3D) printing, to demonstrate their potential for achieving programmable controlled release. A DDS was formulated where the CP provided temporal control over drug release. 3D printing was used to ensure dimensional control over the design of the DDS. The CP used in this study is known to be fragile, and thus was blended with thermoplastic polyurethane (TPU) to achieve a conductive elastomer with sound mechanical properties. Rheological and mechanical analyses were performed, where it was revealed that formulation inks with a storage modulus in the order of 103–104 Pa were both extrudable and maintained their structural integrity. Physico-chemical analysis confirmed the presence of the CP functional groups in the 3D printed DDS. Cyclic voltammetry demonstrated that the DDS remained conductive for 100 stimulations. in vitro drug release was performed for 180 min at varying voltages, where a significant difference (p

IntroductionThe hepatic growth factor (HGF) stimulates DNA synthesis and cell proliferation and plays a role in tissue protection and regeneration. In this study, we have examined the effect of incubation of HGF with urine-derived stem cells (USCs) on the secretion of small extracellular vesicles (sEV) by the cells.Materials and MethodsHGF in the incubation medium was either a bolus administration or a controlled release of an equivalent amount from microbeads within the size range of 50–200 µm made with ultrapurified low-viscosity high-guluronic acid (UP-LVG) alginate. USCs were incubated with or without HGF for 3 days or 7 days before removal of the incubation media, followed by harvesting sEV by the precipitation method. The protein content of isolated sEV was measured by bicinchoninic acid assay (BCA) for these three groups: control (no HGF beads), bolus HGF, and HGF beads. We also performed nanoparticle tracking analysis (NTA), Western blot assay, and ELISA for the HGF content of samples.ResultsWe found a significantly higher concentration of proteins in the HGF microbead group (control release group) compared to the bolus group and the control group after 7 days (p < 0.0017). The NTA data aligned with the BCA; they showed a significantly higher concentration of particles within the size range of sEV (

Abstract Liver fibrosis is a chronic pathological condition lacking specific clinical treatments. Stem cells, with notable potential in regenerative medicine, offer promise in treating liver fibrosis. However, stem cell therapy is hindered by potential immunological rejection, carcinogenesis risk, efficacy variation, and high cost. Stem cell secretome‐based cell‐free therapy offers potential solutions to address these challenges, but it is limited by low delivery efficiency and rapid clearance. Herein, an innovative approach for in situ implantation of smart microneedle (MN) arrays enabling precisely controlled delivery of multiple therapeutic agents directly into fibrotic liver tissues is developed. By integrating cell‐free and platinum‐based nanocatalytic combination therapy, the MN arrays can deactivate hepatic stellate cells. Moreover, they promote excessive extracellular matrix degradation by more than 75%, approaching normal levels. Additionally, the smart MN arrays can provide hepatocyte protection while reducing inflammation levels by ≈70–90%. They can also exhibit remarkable capability in scavenging almost 100% of reactive oxygen species and alleviating hypoxia. Ultimately, this treatment strategy can effectively restrain fibrosis progression. The comprehensive in vitro and in vivo experiments, supplemented by proteome and transcriptome analyses, substantiate the effectiveness of the approach in treating liver fibrosis, holding immense promise for clinical applications.

Progesterone is an endogenous steroid hormone involved in the menstrual cycle, pregnancy, and embryogenesis of humans and other species. Progesterone crystallization techniques have previously reported. Among these techniques, solvent crystallization and different solvent:anti‐solvent systems are considered. Herein, the selective development of either hollow‐like or condensed progesterone microcrystals in elevated yield with controlled polymorphism, habit, and release is described for the first time. For the hollow microcrystals, isopropyl alcohol (IPA) and double‐deionized water (DDW) system is developed as solvent:anti‐solvent, while acetonitrile (AcN) and DDW system are developed for the condensed microcrystals. The microcrystals obtained from both developed crystallization systems are thoroughly investigated with varied microscopic techniques, including brightfield and scanning electron microscopy (SEM), thermal analysis by differential scanning calorimetry (DSC), and crystallography by powder X‐ray diffraction (PXRD) and single XRD, and have been compared. Results show that the crystals of the IPA:DDW crystallization system are hollow and exhibit several habits, whereas the microcrystals of the AcN:DDW crystallization system are more condensed. However, both systems are found to have a wide crystal size distribution of one stable polymorph and are thus highly useful for tunable release. More importantly, these microcrystals exhibit elongated and slow release for 14 days under an expedited release conditions model, indicating suitability for long‐term and potential localized release applications.

Nanotechnology is an emerging field with substantial scientific and economic potential globally. Researchers are increasingly focusing on creating nanomaterials for diverse applications. This review explores the potential of drug-loaded nanofibers for drug delivery and describes their production methods, including centrifugal jet spinning, plasma-induced synthesis, solution blow spinning (SBS), pressure spinning, and electrospinning. Nanofibers, owing to their extensive surface area relative to their volume, are believed to enhance interactions with target substances and therefore are valuable in numerous applications. This review provides a thorough exploration of fabrication techniques, encompassing fundamental concepts, methods, and material aspects. Furthermore, it provides perspectives on the variables affecting the production and application of nanofibers, such as electrospinning parameters (including electric field intensity, needle size, flow rate, and distance between the needle and collector), solution characteristics (such as polymer concentration, solvent type, conductivity, and viscosity), and environmental factors (such as temperature and humidity). Additionally, an extensive compilation of patents related to nanofiber-based drug delivery systems is presented, showcasing innovations and advancements in the field. The review also examines current clinical trials involving nanofiber technologies, providing insights into their therapeutic potential and translational prospects. This review is aimed at presenting an overview of nanofiber drug delivery systems, and identifying future opportunities and challenges in their development and application.

Posterior segment disease acts as a major cause of irreversible visual impairments. Successful treatment of posterior segment disease requires the efficient delivery of therapeutic substances to the targeted lesion. However, the complex ocular architecture makes the bioavailability of topically applied drugs extremely low. Invasive delivery approaches like intravitreal injection may cause adverse complications. To enhance the efficiency, several biomedical engineering systems have been developed to increase the penetration efficiency and improve the bioavailability of drugs at the posterior segments. Advantageously, biodegradable microspheres are found to deliver the therapeutic agents in a controlled fashion. The microspheres prepared from novel biomaterials can realize the prolonged release at the posterior segment with minimum side effects. Moreover, it will be degraded automatically into products that are non-toxic to the human body without the necessity of secondary operation to remove the residual polymer matrix. Additionally, biodegradable microspheres have decent thermoplasticity, adjustable hydrophilicity, controlled crystallinity, and high tensile strength, which make them suitable for intraocular delivery. In this review, we introduce the latest advancements in microsphere production technology and elaborate on the biomaterials that are used to prepare microspheres. We discuss systematically the pharmacological characteristics of biodegradable microspheres and compare their potential advantages and limitations in the treatment of posterior segment diseases. These findings would enrich our knowledge of biodegradable microspheres and cast light into the discovery of effective biomaterials for ocular drug delivery.

Abstract To effectively treat osteoarthritis (OA), the existing inflammation must be reduced before the cartilage damage can be repaired; this cannot be achieved with a single type of extracellular vesicles (EVs). Here, a hydrogel complex with logic‐gates function is proposed that can spatiotemporally controlled release two types of EVs: interleukin 10 (IL‐10)+ EVs to promote M2 polarization of macrophage, and SRY‐box transcription factor 9 (SOX9)+ EVs to increase cartilage matrix synthesis. Following dose‐of‐action screening, the dual EVs are loaded into a matrix metalloporoteinase 13 (MMP13)‐sensitive self‐assembled peptide hydrogel (KM13E) and polyethylene glycol diacrylate/gelatin methacryloyl‐hydrogel microspheres (PGE), respectively. These materials are mixed to form a “microspheres‐in‐gel” KM13E@PGE system. In vitro, KM13E@PGE abruptly released IL‐10+ EVs after 3 days and slowly released SOX9+ EVs for more than 30 days. In vivo, KM13E@PGE increased the CD206+ M2 macrophage proportion in the synovial tissue and decreased the tumor necrosis factor‐α and IL‐1β levels. The aggrecan and SOX9 expressions in the cartilage tissues are significantly elevated following inflammation subsidence. This performance is not achieved using anti‐inflammatory or cartilage repair therapy alone. The present study provides an injectable, integrated delivery system with spatiotemporal control release of dual EVs, and may inspire logic‐gates strategies for OA treatment.

Empagliflozin (EMP) is known for its poor safety and efficacy profile due to its fast body distribution and poor solubility. Accordingly, an oral long-acting and floating/raft-forming nano gel was optimized to release coated EMP nanoparticles, and the released EMP nanoparticles showed enhanced dissolution compared to raw EMP particles. To repurpose EMP for cancer treatment, EMP shows anti-cancer and anti-inflammatory effects against cancer cells. EMP nanoparticles were characterized using FT-IR, PXRD, SEM, EMP encapsulation assay, and release studies. The raft-forming gel encapsulating the EMP was optimized and characterized. The EMP co-polymeric nanoparticles were studied to investigate EMP anti-cancer and anti-inflammatory activities against stomach cancer cells. The solubility of EMP nanoparticles was enhanced in 0.1 N HCl and pH 6.8 by 5 and 12 folds, respectively, compared to raw EMP powder. The particle size and zeta-potential values of improved EMP nanoparticles were 135.40 ± 18.60 nm, and −19.30 ± 0.80 mV, respectively. FT-IR, PXRD, SEM and TEM characterizations revealed polymeric coating of EMP particles. The study suggested that this optimized controlled-release raft-forming gel is a promising local oral approach against stomach cancer. The repurposing of EMP co-polymeric nanoparticles for stomach cancer and associated gastritis treatment was justified.

Guar gum (GG) has drawn more interest from researchers in the last several decades for the controlled delivery of drugs. The aim of the research is to fabricate and evaluate an interpenetrating polymer network (IPN) based nanocarriers system employing chemically modified GG to achieve controlled release of drug. In present study, we have reported the synthesis of carboxymethyl GG-chitosan IPN nanoparticles for controlled release of metformin hydrochloride. Carboxymethyl guar gum (CMGG) was synthesized and employed for developing IPN nanoparticles in combination with chitosan in varying polymeric ratios. A cross-linking agent, sodium tripolyphosphate (Na-TPP) was used for the synthesis of IPN colloidal suspension of nanoparticles which was lyophilized to obtain nanoparticles. The carboxymethylation of GG was confirmed through Fourier transform infra-red spectroscopy. The mean particle size was 440.6 ​nm indicating a polydispersity index of 0.528. The drug entrapment efficiency was found to vary between 67.46 ​± ​1.64 ​% to 88.23 ​± ​2.02 ​%. The differential scanning calorimetry study revealed the presence of amorphous metformin hydrochloride as a homogenous dispersion in nanoparticles (NPs) matrix. In vitro drug release study indicated controlled release ability of developed IPN matrix. A2 formulation (chitosan:CMGG -1:1) exhibited 78.11 ​± ​0.27 ​% release after 8 ​h. Antidiabetic evaluation performed in alloxan-treated diabetic rat model exhibited a prolonged hypoglycemic efficacy over 6 ​h, for A2 formulation treated group, compared to the group receiving only metformin HCl, which demonstrated a reduction in blood glucose levels for up to 4 ​h. The study findings demonstrated the efficacy of the CMGG-chitosan based IPN nanoparticulate system for sustained delivery of therapeutic agents.

Additive manufacturing offers manufacture of personalised pharmaceutical tablets through design freedoms and material deposition control at an individual voxel level. This control goes beyond geometry and materials choices: inkjet based 3D printing enables the precise deposition (10–80 μm) of multiple materials, which permits integration of precise doses with tailored release rates; in the meanwhile, this technique has demonstrated its capability of high-volume personalised production. In this paper we demonstrate how two dissimilar materials, one water soluble and one insoluble, can be co-printed within a design envelope to dial up a range of release rates including slow (0.98 ± 0.04 mg/min), fast (4.07 ± 0.25 mg/min) and multi-stepped (2.17 ± 0.04 mg/min then 0.70 ± 0.13 mg/min) dissolution curves. To achieve this, we adopted poly-4-acryloylmorpholine (poly-ACMO) as a new photocurable water-soluble carrier and demonstrated its contemporaneous deposition with an insoluble monomer. The water soluble ACMO formulation with aspirin incorporated was successfully printed and cured under UV light and a wide variety of shapes with material distributions that control drug elution was successfully fabricated by inkjet based 3D printing technique, suggesting its viability as a future personalised solid dosage form fabrication routine.

Conventional cancer chemotherapy regimens, albeit successful to some extent, suffer from some significant drawbacks, such as high-dose requirements, limited bioavailability, low therapeutic indices, emergence of multiple drug resistance, off-target distribution, and adverse effects. The main goal of developing implantable drug delivery systems (IDDS) is to address these challenges and maintain anti-cancer drugs directly at the intended sites of therapeutic action while minimizing inevitable side effects. IDDS possess numerous advantages over conventional drug delivery, including controlled drug release patterns, one-time drug administration, as well as loading and stabilizing poorly water-soluble chemotherapy drugs. Here, we summarized conventional and novel (three-dimensional (3D) printing and microfluidic) preparation techniques of different IDDS, including nanofibers, films, hydrogels, wafers, sponges, and osmotic pumps. These systems could be designed with high biocompatibility and biodegradability features using a wide variety of natural and synthetic polymers. We also reviewed the published data on these systems in cancer therapy with a particular focus on their release behavior. Various release profiles could be attained in IDDS, which enable predictable, adjustable, and sustained drug releases. Furthermore, multi-step or stimuli-responsive drug release could be obtained in these systems. The studies mentioned in this article have proven the effectiveness of IDDS for treating different cancer types with high prevalence, including breast cancer, and aggressive cancer types, such as glioblastoma and liver cancer. Additionally, the challenges in applying IDDS for efficacious cancer therapy and their potential future developments are also discussed. Considering the high potential of IDDS for further advancements, such as programmable release and degradation features, further clinical trials are needed to ensure their efficiency. The overall goal of this review is to expand our understanding of the behavior of commonly investigated IDDS and to identify the barriers that should be addressed in the pursuit of more efficient therapies for cancer.

Abstract Diabetic retinopathy (DR) is a condition that causes swelling of the blood vessels of the retina and leaks blood and fluids. It is the most severe form of diabetic eye disease. It causes vision loss in its advanced stage. Diabetic retinopathy is responsible for causing 26% of blindness. Very insufficient therapies are accessible for the treatment of DR. As compared to the conventional therapies, there should be enhanced research on the controlled release, shorter duration, and cost-effective therapy of diabetic retinopathy. The expansion of advanced nanocarriers-based drug delivery systems has been now employed to exploit as well as regulate the transport of many therapeutic agents to target sites via the increase in penetration or the extension of the duration of contact employing production by enclosing as well as distributing tiny molecules in nanostructured formulation. Various polymers have been utilized for the manufacturing of these nanostructured formulations. Chitosan possesses incredible biological and chemical properties, that have led to its extensive use in pharmaceutical and biomedical applications. Chitosan has been used in many studies because of its enhanced mucoadhesiveness and non-toxicity. Multiple studies have used chitosan as the best candidate for manufacturing nanocarriers and treating diabetic retinopathy. Numerous nanocarriers have been formulated by using chitosan such as nanostructured lipid carriers, solid lipid nanoparticles, liposomes, and dendrimers for treating diabetic retinopathy. This current review elaborates on the recent advancements of chitosan as a promising approach for the manufacturing of nanocarriers that can be used for treating diabetic retinopathy.

Polymer-based hydrogels are hydrophilic polymer networks with a remarkable capacity to absorb substantial amounts of water and biological fluids, rendering them highly attractive for drug delivery applications. The COVID-19 pandemic has acted as a catalyst for research and innovation in the realm of polymer-based hydrogels for drug delivery, with a particular emphasis on antiviral therapeutics, vaccines, diagnostics, and precision delivery to the respiratory system. The distinctive attributes of hydrogels, such as their biocompatibility, customizable drug release profiles, and ease of functionalization, establish them as versatile platforms for the development of advanced drug delivery systems to combat not only COVID-19 but also a spectrum of other infectious diseases. This study is dedicated to scruti-nizing and evaluating the characteristics of polymer-based hydrogels employed in drug delivery for the treatment of diseases associated with the SARS-CoV-2 virus. Furthermore, the investigation introduces a novel classification system for polymer-based hydrogels deployed in drug delivery for SARS-CoV-2-related diseases. Additionally, the paper provides an up-to-date evaluation of the latest developed hydrogels utilized in drug delivery for the treatment of dis-eases linked to the SARS-CoV-2 virus, based on research conducted through the recent months of 2023.

Environment-responsive hydrogels are environmentally friendly polymeric materials that rapidly respond to their environment by changing their volume or strength when the external environment, such as temperature, pH, light, and magnetism, changes. As environment-responsive hydrogels, they are uniquely flexible and sensitive, enabling them to be used in various applications, and are now at the forefront of polymer science research. Scholars have reviewed more environmentresponsive hydrogels in biomedicine, detection sensors, and drug release. We present a detailed description of the reaction mechanism and preparation process of environment-responsive hydrogels, taking temperature-responsive, pH-responsive, and light-responsive hydrogels as examples. Finally, a summary is given at the end: 1) the application of environmentally responsive hydrogels in agriculture, and 2) the problems and future trends of their application in agriculture.

Polymer-ceramic hybrid nanoparticles have emerged as promising platforms for controlled drug release applications. By integrating organic polymers with inorganic ceramics at the nanoscale, hybrid nanoparticles exhibit tailored properties for the efficient encapsulation and programmed release of therapeutic agents. The ceramic domains impart structural rigidity and controlled release kinetics while the polymeric phases facilitate processing, functionalisation and a stimuli-responsive release. Various fabrication methods enable the optimisation of the nanoparticle size, shape, composition and surface properties. Drugs can be loaded through encapsulation, absorption and dispersion, and released via diffusion, swelling, erosion and stimuli-triggered mechanisms. Hybrid nanoparticles have shown potential for tumour therapy through passive and active targeting, as well as tissue engineering by providing the sustained delivery of growth factors and stem cells. However, challenges remain regarding the drug loading capacity, release control, particle stability and toxicity, requiring further research efforts to fully realise the possibilities of polymer-ceramic hybrid nanoparticles for next-generation drug delivery.

Abstract Development of nano-enabled fertilizers from green waste is one of the effective options to enhance global agricultural productions and minimize environmental pollution. In this study, novel, eco-friendly and cost-effective nano- enabled fertilizers (NEF) were synthesized using the planetary ball milling procedure. The NEF (nDPF1and nDPF2) were prepared by impregnation of nanostructured date palm pits (nDPP) with (KH2PO4 + MgO) at 1:1 and 3:1 (w/w) ratios respectively. The nDPP, nDPF1 and nDPF2 were extensively characterized. The produced nano-fertilizers enhanced soil water retention capacity with nDPF2 being the most effective. The water retention capacity of nDPF2 treated soil was 5.6 times higher than that of soil treated with conventional fertilizers. In addition, the nDPF2 exhibited superior sustained lower release rates of P, K and Mg nutrients for longer release periods in comparison with the conventional fertilizers. For instance, P cumulative release percentages from conventional fertilizers, nDPF1 and nDPF2 in soil reached 22.41%, 10.82 and 8.9% respectively within 384 h. Findings from FTIR and XPS analyses suggested that hydrogen bonding and ligand exchange were the main interaction mechanisms of PO4-K-Mg ions with nDPP surface. The released kinetics data of the NEF revealed that power function was the best suitable model to describe the kinetics of P, K and Mg release data from NEF in water and soil. Pot study ascertained that the nano-enabled fertilizers (nDPF1 and nDPF2) significantly promoted biomass production and nutrient uptake of maize plants as compared to commercial fertilizer treated plants. The present work demonstrated the potential of NEF to increase nutrients uptake efficiency, mitigate moisture retention problem in arid soils and reduce nutrients loss through leaching and safeguard the environment. Graphical Abstract

Abstract Successful oral insulin administration can considerably enhance the quality of life (QOL) of diabetes patients who must frequently take insulin injections. Oral insulin administration, on the other hand, is seriously hampered by gastrointestinal enzymes, wide pH range, mucus and mucosal layers, which limit insulin oral bioavailability to ≤ 2%. Therefore, a large number of technological solutions have been proposed to increase the oral bioavailability of insulin, in which polymeric nanoparticles (PNPs) are highly promising for oral insulin delivery. The recently published research articles chosen for this review are based on applications of PNPs with strong future potential in oral insulin delivery, and do not cover all related work. In this review, we will summarize the controlled release mechanisms of oral insulin delivery, latest oral insulin delivery applications of PNPs nanocarrier, challenges and prospect. This review will serve as a guide to the future investigators who wish to engineer and study PNPs as oral insulin delivery systems. Graphical Abstract

The aim of the present work was to show the sustainability of fibrin sealant in releasing dexamethasone and adjust the protocol for clinical application of the novel method in the treatment of Meniere's disease (MD) and sudden sensorineural hearing loss (SSHL). Gelation occurred shortly after mixing dexamethasone-containing fibrinogen with thrombin. Dexamethasone was constantly released for at least 16 d at a stable level after 7 d in protocol 1 (low-dose), while it was robustly released within 4 d and slowed afterward until 10 d in protocol 2 (high-dose). There were significant differences among the time points in Protocol 2 (p

Min Chen,1,&ast; Tao Liu,2,&ast; Wenqiang Li,3 Yingting Li,1 Puxin Zhong,1 Huanchen Yan,1 Jingyin Kong,1 Weixiang Liang2 1Department of Obstetrics and Gynecology, Department of Fetal Medicine and Prenatal Diagnosis; Guangdong Provincial Key Laboratory of Major Obstetric Diseases; Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology; Guangdong-Hong Kong-Macao Greater Bay Area Higher Education Joint Laboratory of Maternal-Fetal Medicine; The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510000, People’s Republic of China; 2Department of Ultrasound; Guangdong Provincial Key Laboratory of Major Obstetric Diseases; Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology; The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510000, People’s Republic of China; 3Engineering Technology Research Center for Sports Assistive Devices of Guangdong, Guangzhou Sport University, Guangzhou, 510076, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Min Chen, Email edchen99@gmail.comBackground: Cartilage-related diseases, such as hypoplastic chondrodysplasia a rare genetic disorder that affects newborns, causing abnormal cartilage development and restricted skeletal growth. However, the development of effective treatment strategies for chondrodysplasia still faces significant challenges due to limitations in the controlled drug delivery, biocompatibility, and biodegradability of nanomedicines.Methods: A biodegradable magnesium doped-silicon based-nanoplatforms based on silicon nanoparticles (MON) was constructed. Briefly, the MON was modified with sulfhydryl groups using MPTMS to form MOS. Further engineering of MOS was achieved by incorporating Mg2+ ions through the “dissolution-regrowth” method, resulting in MMOS. Ica was effectively loaded into the MMOS channels, and HA was anchored on the surface of MOS to obtain MMOS-Ica@HA nanoplatforms. Additionally, in vitro cell experiments and in vivo zebrafish embryo models were used to evaluate the effect of the nanoplatforms on cartilage differentiation or formation and the efficiency of treating chondrodysplasia.Results: A series of characterization tests including TEM, SEM, DLS, XPS, EDX, and BET analysis validate the successful preparation of MOS-Ica@HA nanoplatforms. The prepared nanoplatforms show excellent dispersion and controllable drug release behavior. The cytotoxicity evaluation reveals the good biocompatibility of MOS-Ica@HA due to the sustained and controllable release of Ica. Importantly, the presence of Ica and Mg component in MOS-Ica@HA significantly promote chondrogenic differentiation of BMSCs via the Smad5/HIF-1α signaling pathway. In vitro and in vivo experiments confirmed that the nanoplatforms improved chondrodysplasia by promoting cartilage differentiation and formation.Conclusion: The findings suggest the potential application of the developed biodegradable MMOS-Ica@HA nanoplatforms with acceptable drug loading capacity and controlled drug release in chondrodysplasia treatment, which indicates a promising approach for the treatment of chondrodysplasia.Keywords: nanoplatforms, controlled release, biocompatibility, chondrodysplasia, cartilage differentiation

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.

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.

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.

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.

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.

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.

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.

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.