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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.

Essential oils (EOs) are versatile natural compounds with significant antimicrobial, antioxidant, antifungal, and therapeutic properties, making them valuable in industries such as food preservation, agriculture, and healthcare. However, their inherent volatility, low water solubility, and susceptibility to environmental degradation limit their direct applications. Nanotechnology offers transformative solutions to these challenges, enhancing the stability, bioavailability, and efficacy of EOs through innovative nano systems such as nano emulsions, encapsulations, and nanocomposites. This study explores the integration of nanotechnology with essential oils, emphasizing advanced preparation techniques, physicochemical properties, and diverse applications. It highlights sustainable approaches, including eco-friendly synthesis and biodegradable carriers, which align with global trends toward green chemistry. By addressing key challenges and proposing future directions, this research underscores the potential of EO nano systems to deliver multifunctional and environmentally conscious solutions for global challenges such as food security, antimicrobial resistance, and sustainable agriculture. [ABSTRACT FROM AUTHOR]

The aim of this study was to compare the effect of increasing concentrations (0, 1, 2, 4%) of sea buckthorn oil (SBO) on the structural, physicochemical, release, and antioxidant properties of glycerol-plasticized sodium casein (NaCAS) and gelatin (GEL) films. Ultrasonic treatment ensured effective homogenization of SBO in both types of emulsions, resulting in yellow-tinted semi-opaque films with relatively low micro-roughness. Generally, GEL films demonstrated lower UV barrier properties and solubility but exhibited higher compactness, crystallinity, transparency, surface hydrophobicity, oxygen barrier performance, strength, and antiradical activity compared to their NaCAS-based counterparts. In a concentration-dependent manner, SBO decreased the solubility and water absorption of the gelatin-based film and enhanced its oxygen permeability. Conversely, SBO improved the water vapor barrier properties of both films in a concentration-independent manner. At the highest SBO concentration, the tensile strength of NaCAS- and GEL-based films decreased by 27% and 20%, respectively, while their antiradical activity increased by 9.3× and 4.3× (based on the time required for the half-neutralization of 2,2-diphenyl-1-picrylhydrazyl radicals). Migration studies showed that at the lowest concentration, SBO was released (into 95% ethanol) approximately 2× faster from the GEL-based film than from the NaCAS film, whereas at higher concentrations, the trend reversed. [ABSTRACT FROM AUTHOR]

Functional foods play a crucial role in contemporary dietary strategies. This study investigates the incorporation of oregano oil, a bioactive extract that is known for its antimicrobial and antioxidant properties, into gelatin-based gummy jellies to develop functional food products with controlled release properties. The jellies were evaluated for mass uniformity, swelling index, disintegration time, and tensile strength under simulated oral and gastric conditions. The results showed that oregano oil significantly reduced the swelling index (e.g., 128.76 ± 0.67% at pH 5) and prolonged the disintegration time (e.g., 6–18 min across pH environments), highlighting its potential for controlled release. The mechanical strength remained stable (5.2 ± 0.3 N), ensuring structural integrity. These findings suggest that oregano-oil-enriched gummy jellies offer health benefits, although further studies are needed to explore their long-term stability and bioavailability. [ABSTRACT FROM AUTHOR]

Albendazole (ABZ), classified as a class II basic drug under the Biopharmaceutics Classification System (BCS), is widely recognized for its therapeutic efficacy in treating and preventing trichuriasis. However, despite its clinical relevance, ABZ's oral administration presents challenges due to its poor solubility and pH sensitivity, which diminish its therapeutic effectiveness. Additionally, high dosing regimens of ABZ pose risks of developmental toxicity in animal models. This study developed a pH-sensitive solid dispersion of albendazole (ABZ-pHs-SD) using Glyceryl Monostearate (GM) in conjunction with Hypromellose Acetate Succinate (HPMC-AS). Characterization via Scanning Electron Microscopy (SEM), Powder X-ray Diffraction (PXRD), Differential Scanning Calorimetry (DSC), and Fourier Transform Infrared Spectroscopy (FT-IR) confirmed the high dispersion of ABZ in a crystalline state within the carrier. Furthermore, we compared the in vitro dissolution profile, pharmacokinetics, and intestinal drug concentration of ABZ-pHs-SD with commercially available formulations. Our findings demonstrated that ABZ-pHs-SD exhibited an excellent dissolution profile, significantly increasing the solubility of ABZ in water by 3.15 times. The formulation effectively prevented drug release in acidic environments while maintaining a slow release in weakly alkaline conditions. Additionally, compared to commercial formulations, ABZ-pHs-SD showed significantly lower Cmax (4.70 ± 1.16 vs. 6.83 ± 0.66 μg/mL) and higher Tmax (5.5 ± 0.93 vs. 3.75 ± 0.71 h) in vivo , achieving elevated drug concentration levels in the cecal and colonic environments (p < 0.01) without significantly decreasing bioavailability. Overall, our research findings indicate that ABZ-pHs-SD serves as a promising drug delivery strategy for the poorly soluble and pH-sensitive ABZ. Particularly, the simple preparation of solid dispersion demonstrates strong industrial feasibility. [ABSTRACT FROM AUTHOR]

Cardiovascular diseases such as myocardial infarction or limb ischemia are characterized by regression of blood vessels. Local delivery of growth factors (GFs) involved in angiogenesis such as fibroblast blast growth factor-2 (FGF-2) has been shown to trigger collateral neovasculature and might lead to a therapeutic strategy. In vivo, heparin, a sulfated polysaccharide present in abundance in the extracellular matrix (ECM), has been shown to function as a local reservoir for FGF-2 by binding FGF-2 and other morphogens and it plays a role in the evolution of GF gradients. To access injectable biomaterials that can mimic such natural electrostatic interactions between soluble signals and macromolecules and mechanically tunable environments, the backbone of agarose, a thermogelling marine–algae-derived polysaccharide, was modified with sulfate, phosphate, and carboxylic moieties and the interaction and release of FGF-2 from these functionalized hydrogels was assessed by ELISA in vitro and CAM assay in ovo. Our findings show that FGF-2 remains active after release, and FGF-2 release profiles can be influenced by sulfated and phosphorylated agarose, and in turn, promote varied blood vessel formation kinetics. These modified agaroses offer a simple approach to mimicking electrostatic interactions experienced by GFs in the extracellular environment and provide a platform to probe the role of these interactions in the modulation of growth factor activity and may find utility as an injectable gel for promoting angiogenesis and as bioinks in 3D bioprinting. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to synthesize polylactic acid (PLA) nanofibrillar scaffolds loaded with ibuprofen (IBU) using electrospinning (ES) and air-jet spinning (AJS). The scaffolds were evaluated for their physicochemical properties, drug release profiles, and biocompatibility to assess their potential for local analgesic applications. Methods: Solutions of 10% (w/v) PLA combined with IBU at concentrations of 10%, 20%, and 30% were processed into nanofibrillar membranes using ES and AJS. The scaffolds were characterized using scanning electron microscopy (SEM), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), and Fourier-transformed infrared (FT-IR) spectroscopy. The drug release profile was assessed by ultraviolet-visible spectrophotometry (UV-Vis), and cell adhesion and viability were evaluated using fibroblast culture assays. Statistical analyses included qualitative analyses, t-tests, and Likelihood ratio tests. Results: SEM revealed randomly arranged nanofibers forming reticulated meshes, with more uniform dimensions observed in the AJS group. TGA and DSC analyses confirmed the thermodynamic stability of the scaffolds and enthalpy changes consistent with IBU incorporation, which FT-IR and UV-Vis validated. Drug release was sustained over 384 h, showing no significant differences between ES and AJS scaffolds (p > 0.05). Cytotoxicity and cell viability assays confirmed scaffold biocompatibility, with cellular responses proportional to drug concentration but within safe limits. Conclusions: PLA-IBU nanofibrillar scaffolds were successfully synthesized using ES and AJS. Both methods yielded biocompatible systems with stable properties and controlled drug release. Further, in vivo studies are necessary to confirm their clinical potential. [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]

The present study evaluates the effect of PEG content on the characteristics of poly(lactic-co-glycolic acid)-polyoxyethylene (PLGA-PEG) microspheres loaded with a small molecular weight drug on the polymer matrix degradation behavior of the polymeric matrix and drug release profile. Aclacinomycin A (ACM) was encapsulated in PLGA-PEG microspheres with varying PEG content (0%, 5%, 10%, or 15%) using the oil-in-water solvent evaporation method. Microspheres were obtained with sizes ranging from 45–70 mm, drug loading around 1.3% and encapsulation efficiencies between 48–70%. The produced microspheres were further characterized in terms of degradation behavior and drug release kinetics. The results showed that while PEG content had minimal impact on drug loading and microsphere size, it significantly influenced the degradation behavior of the microspheres and its weight in the release process. In vitro drug release profiles exhibited a three-phase pattern for all PLGA-PEG microspheres with faster and more extensive ACM release compared to PLGA microspheres, being the release improved with the PEG content increase. The Corrigan model was successfully applied to the release data yielding burst-phase kinetic constants (kb) between 0.082–0.288 and degradation/erosion kinetic constants (k) between 0.054–0.093 day−¹, both of which increased with higher PEG content. [ABSTRACT FROM AUTHOR]

Researchers have been investigating the physical and morphological properties of biodegradable polymer and copolymer films, blending them with other chemicals to solve challenges in medical, industrial, and eco-environmental fields. The present study introduces a novel, straightforward method for preparing biodegradable hydrogels based on polyvinyl alcohol (PVA) and polyvinyl pyrrolidone (PVP) for medical applications. The resulting PVA/PVP-based hydrogel uniquely combines the water absorbency, biocompatibility, and biodegradability of the polymer composite. For hygiene products and medical uses, such as wound healing, hydrogen peroxide (HP) was encapsulated in the PVA/PVP hydrogels for controlled release application. Incorporating PVP into PVA significantly enhances the hydrogel water absorbency and improves the mechanical properties. However, to mitigate the disadvantage of high water absorbency which could result in undesired early dissolution, efforts were made to increase the water resistance and the mechanical characteristics of these hydrogels using freeze–thaw (F/T) cycles and chemical crosslinking PVA chains with trisodium trimetaphosphate (STMP). The resulting hydrogels serve as environmentally friendly bio-based polymer blends, broadening their applications in medical and industrial products. The structural and morphological properties of the hydrogel were characterized using Fourier transform infrared spectroscopy (FTIR), environmental scanning electron microscope analysis (E-SEM), and water-swelling tests. The HP controlled release rate was evaluated through kinetic release experiments using the ex vivo skin model. The antibacterial activity of the hydrogel films was examined on four medically relevant bacteria: Staphylococcus aureus, Enterococcus faecalis, Escherichia coli, and Pseudomonas aeruginosa, with an adapted disk diffusion assay. Using this assay, we also evaluated the antibacterial effect of the hydrogel films over the course of days, demonstrating the HP controlled release from these hydrogels. These findings support further in vivo investigation into controlled HP release systems for improved wound-healing outcomes. [ABSTRACT FROM AUTHOR]

Background/objectives: The aim of the study was to create a nanofiber insert incorporating Timolol (TIM) and Dorzolamide (DOR), targeting the management of glaucoma. This condition encompasses a variety of chronic, advancing ocular disorders typically associated with elevated intraocular pressure (IOP). Methods: The insert was made of Eudragite RL100 (EUD) polymer, a biocompatible material with high bioavailability, using the electrospinning method. The inserts were studied for morphology, drug–polymer interaction, physicochemical properties, and in vitro drug-release study. The pharmacokinetic properties of fibers were examined alongside consideration for irritation using a rabbit model and cell compatibility. Results: The results of the in vitro drug-release test showed retention and controlled release of both DOR/TIM over 80 h. Morphological examination demonstrated uniform nanofibers with mean diameters < 465 nm. The cell compatibility test showed a high percentage of cell survival, and none of the formulations irritated the rabbit's eye. The Area Under the Curve (AUC0-72) for DOR and TIM in EDT formulations was approximately 3216.63 ± 63.25 µg·h/mL and 2598.89 ± 46.65 µg·h/mL, respectively, with Mean Residence Times (MRTs) of approximately 21.6 ± 0.19 h and 16.29 ± 6.44 h. Conclusions: Based on the results, the dual drug-loaded nanofiber preservative-free system can potentially be a suitable alternative to eye drops and can be used to reduce fluctuation and dose frequency. [ABSTRACT FROM AUTHOR]

The main objective of the current research work was to synthesize mesoporous silica nanoparticles for controlled delivery of mometasone furoate for potential nasal delivery. The optimized sol–gel method was used for the synthesis of mesoporous silica nanoparticles. Synthesized nanoparticles were processed through Zeta sizer, SEM, TEM, FTIR, TGA, DSC, XRD, and BET analysis for structural characterization. The in vitro dissolution test was performed for the inclusion compound, while the Franz diffusion experiment was performed for permeability of formulation. For the determination of expression levels of anti-inflammatory cytokines IL-4 and IL-5, RNA extraction, reverse transcription, and polymerase chain reaction (RT-PCR) were performed. The MTT assay was also performed to determine cell viability. Synthesized and functionalized mesoporous silica nanoparticles showed controlled release of drugs. FT-IR spectroscopy confirmed the presence of the corresponding functional groups of drugs within mesoporous silica nanoparticles. Zeta sizer and thermal analysis confirmed the delivery system was in nano size and thermally stable. Moreover, a highly porous system was observed during SEM and TEM evaluation, and further it was confirmed by BET analysis. Greater cellular uptake with improved permeability characteristics was also observed. As compared to the crystalline drug, a significant improvement in the dissolution rate was observed. It was concluded that stable mesoporous silica nanoparticles with significant porosity were synthesized, efficiently delivering the loaded drug without any toxic effect. [ABSTRACT FROM AUTHOR]

Diabetic wound healing presents unique challenges, including impaired angiogenesis, prolonged inflammation, and delayed re‐epithelialization. Advancements in tissue engineering offer promising solutions through cell/drug‐based therapies. Exosomes (Exo) derived from hypoxia‐preconditioned adipose‐derived stem cells (ADSCs) have gained attention for their potential to address these complex issues in diabetic wounds. Existing strategies for Exo delivery aim to overcome drawbacks associated with conventional administration methods, including rapid loss of activity, frequent dosing, and off‐target effects. However, complexities in fabrication, undesirable components within the delivery system, and unforeseen outcomes have hindered the efficacy of these approaches. Thus, an in situ formed hydrogel is engineered using click chemistry to facilitate the convenient encapsulation of hypoxia‐induced Exo. The hydrogel swiftly transitioned into a gel state upon mixing and facilitated the controlled release of Exo at various loading dosages. Through systematic screening of Exo‐hydrogel formulations, it is demonstrated that the encapsulated Exo retained their bioactivity, exhibits therapeutic efficacy in vitro via scratch and tube formation assays. Further, the optimal Exo‐hydrogel promotes accelerated wound healing while preventing scar formation in a diabetic rat wound model. The Exo‐loaded hydrogel represents a promising approach for efficient Exo delivery in wound healing applications and holds potential for broader applications in diverse medical fields. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is recognized as a highly friction‐related joint disease primarily associated with increased joint friction and inflammation due to pro‐inflammatory M1‐type macrophage infiltration in the articular cavity. Therefore, strategies to simultaneously increase lubrication and relieve inflammation to remodel the damaged articular microenvironment are of great significance for enhancing its treatment. Herein, a multifunctional core‐brush nanoplatform composed of a ROS‐scavenging polydopamine‐coated SiO2 core and lubrication‐enhancing zwitterionic poly(2‐methacryloyloxyethyl phosphorylcholine) (PMPC) brush and loaded with the anti‐inflammatory drug curcumin by a reactive oxygen species (ROS)‐liable conjugation (named as SiO2@PP‐Cur) is rationally designed. Benefiting from the grafted zwitterionic PMPC brush, a tenacious hydration layer with enhanced lubricity for reducing joint abrasions is developed. More importantly, based on the mono‐iodoacetic acid‐induced arthritis (MIA) rat model, intra‐articular injection of SiO2@PP‐Cur nanoplatform can effectively alleviate articular inflammation via promoting macrophage polarization from the pro‐inflammatory M1 to anti‐inflammatory M2 state by activating the nuclear factor erythroid 2‐related factor 2 (Nrf2) signaling pathway and attenuating the degradation of cartilage matrix, resulting in the remodeling of the damaged microenvironment into a pro‐regenerative microenvironment. As a result, SiO2@PP‐Cur can considerably inhibit OA progression. Therefore, the work may provide a novel strategy for the development of an advanced core‐brush nanoplatform for enhanced OA therapy. [ABSTRACT FROM AUTHOR]

Emamectin benzoate (EB) is a highly effective broad-spectrum insecticide and acaricide. However, because EB is easily degraded, the conventional formulations of EB are often overapplied. In this study, polylactic acid (PLA)-based microspheres were prepared using the modified solvent evaporation method for the controlled release of EB. The microspheres were optimized to achieve higher EB loading. The effects of process parameters on the properties of microspheres, including encapsulation efficiency (EE), particle size, and pesticide loading, were investigated. Additionally, the controlled release behavior of EB microspheres was compared with that of conventional EB emulsifiable concentrate (EC). Spherical-shaped microspheres were obtained with an EE reaching 90.63 ± 1.90%, and introducing an external aqueous phase into the system can significantly enhance the EE of microspheres by over 30%. FTIR, DSC, and XRD analyses indicate that the preparation process of PLA microspheres was mainly physical encapsulation and had no chemical effect on EB. Notably, the EB microspheres displayed more potent control efficacy compared to commercial formulation EB EC against Plutella xylostella. The corrected mortality for the EB microspheres reached 90.00 ± 5.77% after 21 days of application, whereas the corrected mortality for the EB EC was only 19.23 ± 6.66% after 14 days of application. Our study demonstrates that EB-encapsulated PLA microspheres have strong potential as environmentally friendly control release EB formulations. [ABSTRACT FROM AUTHOR]

Antioxidants are contained in fruits and vegetables and are commonly obtained through food. However, it is frequently necessary to supplement the diet with substances that are often poorly soluble in water and sensitive to light and oxygen. For this reason, in this work, luteolin (LUT) and naringenin (NAR), two compounds with antioxidant activity and potential health benefits, were precipitated through the supercritical antisolvent technique using polyvinylpyrrolidone and β-cyclodextrin as the carriers. The precipitation occurred from dimethylsulfoxide using supercritical carbon dioxide as the antisolvent. The influence of pressure (9–12 MPa), active substance/carrier concentration in the solution (20–200 mg/mL), and their ratio (1/1 and 1/2 mol/mol) on morphology, particle mean size, and distribution were investigated. Under the optimized operating conditions, spherical microparticles with a mean diameter equal to 2.7 ± 0.9 μm (for LUT) and 5.5 ± 1.9 μm (for NAR) were obtained. The active ingredients were protected from the external environment by the presence of the carrier, and the dissolution rate was notably increased by processing them with β-cyclodextrin. It was sixty times faster and three times faster than that of the antioxidant alone for LUT and NAR, respectively. [ABSTRACT FROM AUTHOR]

Although a lot of recent research revealed advantages of novel biopolymers' implementation as active food packaging polymers, there is not an equivalent effort from industry to use such films, probably because of the required cost to change the supply chain and the equipment. This study investigates the use of two natural abundant nanoclays, laponite (Lap) and montmorillonite (Mt), as eugenol slow-release carriers for enhancing the functionality of low-density polyethylene (LDPE) active packaging films. The target is to combine the spirit of the circular economy with the existent technology and the broadly used materials to develop a novel attractive product for active food packaging applications. Utilizing a vacuum-assisted adsorption method, eugenol was successfully intercalated into Lap and Mt nanoclays, forming EG@Lap and EG@Mt nanohybrids. Testing results confirmed effective integration and dispersion of the nanohybrids within the LDPE matrix. The most promising final film seems to be the LDPE with 15% w/w EG@Lap nanohybrid which exhibited a higher release rate (k2 = 5.29 × 10−4 s−1) for temperatures ≤70 °C, similar mechanical properties, a significantly improved water barrier (Dwv = 11.7 × 10−5 cm2·s−1), and a slightly improved oxygen barrier (PeO2 = 2.03 × 10−8 cm2·s−1) compared with neat LDPE. Antimicrobial and sensory tests on fresh minced pork showed two days' shelf-life extension compared to pure LDPE and one more day compared to LDPE with 15% w/w EG@Mt nanohybrid. [ABSTRACT FROM AUTHOR]

Centella asiatica L. extract is a promising natural agent for the treatment of atopic dermatitis. It significantly reduces inflammation due to its immunomodulatory properties, mainly attributed to the presence of pentacyclic triterpenes, namely madecassoside and asiaticoside. Their incorporation into sustainable cold-processed topical formulations, such as emollient-rich emulsions and cosmetic gel containing natural hydrophilic polymers, should inhibit inflammation in atopic skin. Therefore, the objective of this study is to investigate the controlled release of madecassoside and asiaticoside isolated from Centella asiatica L., loaded into topical formulations, namely emollient-rich O/W and W/O emulsions and cosmetic gel, which could support the treatment of atopic dermatitis. The carriers of active substances have been prepared with sustainable emulsifiers, active substances, and emollients obtained by green technologies from food industry wastes. Low-energy methods during the carrier emulsification process were applied to reduce carbon footprints and preserve the valuable properties of the raw materials used. The influence of the Centella asiatica L. extract on the physicochemical properties of the formulations was studied, showing a satisfactory degree of stability of the formulations obtained. Moreover, factors that may influence the mechanism and kinetics of the release of madecassoside and asiaticoside, such as the concentration of the active substance, the pH of the dissolution medium, and the type of the carrier, have been tested and widely discussed. [ABSTRACT FROM AUTHOR]

Background/Objectives: Doxorubicin (Dox) is an anticancer drug used in the treatment of a wide range of solid tumors; however, Dox causes systemic toxicity and irreversible cardiotoxicity. The design of a new nanosystem that allows for the control of Dox loading and delivery results is a powerful tool to control Dox release only in cancer cells. For this reason, supramolecular self-assembly was performed between a poly(amidoamine) (PAMAM) dendrimer decorated with four β-cyclodextrin (βCD) units (PAMAM-βCD) and an adamantane–hydrazone–doxorubicin (Ad-h-Dox) prodrug. Methods: The formation of inclusion complexes (ICs) between the prodrug and all the βCD cavities present on the surface of the PAMAM-βCD dendrimer was followed by 1H-NMR titration and corroborated by 2D NOESY experiments. A full characterization of the supramolecular assembly was performed in the solid state by thermal analysis (DSC/TGA) and scanning electron microscopy (SEM) and in solution by the DOSY NMR technique in D2O. Furthermore, the Dox release profiles from the PAMAM-βCD/Ad-h-Dox assembly at different pH values was studied by comparing the efficiency against a native βCD/Ad-h-Dox IC. Additionally, in vitro cytotoxic activity assays were performed for the nanocarrier alone and the two supramolecular assemblies in different carcinogenic cell lines. Results: The PAMAM-βCD/Ad-h-Dox assembly was adequately characterized, and the cytotoxic activity results demonstrate that the nanocarrier alone and its hydrolysis product are innocuous compared to the PAMAM-βCD/Ad-h-Dox nanocarrier that showed cytotoxicity equivalent to free Dox in the tested cancer cell lines. The in vitro drug release assays for the PAMAM-βCD/Ad-h-Dox system showed an acidic pH-dependent behavior and a prolonged profile of up to more than 72 h. Conclusions: The design of PAMAM-βCD/Ad-h-Dox consists of a new controlled and prolonged Dox release system for potential use in cancer treatment. [ABSTRACT FROM AUTHOR]

Background: Psoriatic arthritis (PsA), a chronic inflammatory disease, mainly affects the joints, with approximately 30% of psoriasis patients eventually developing PsA. Characterized by both innate and adaptive immune responses, PsA poses significant challenges for effective treatment. Recent advances in drug delivery systems have sparked interest in developing novel formulations to improve therapeutic outcomes. The current research focuses on the development and evaluation of a nanosponge-loaded, cyclo-oxygenase-2 (COX-2) inhibitor-based topical gel for the treatment of PsA. Methods: Nanosponges (NSs) were prepared by using beta-cyclodextrin as a polymer and dimethyl carbonate (DMC) as a crosslinker by melting, and gels were prepared by employing carbopol and badam gum as polymers. Results: Solubility studies confirmed that the prepared nanosponges were highly soluble. FT-IR studies confirmed the formation of hydrogen bonds between lumiracoxib and beta-cyclodextrin. SEM confirmed that the prepared formulations were roughly spherical and porous in nature. The average particle size was 190.5 ± 0.02 nm, with a zeta potential of −18.9 mv. XRD studies showed that the crystallinity of lumiracoxib decreased after encapsulation, which helped to increase its solubility. The optimized nanosponges (NS2) were incorporated in an optimized gel (FG10) to formulate a nanosponge-loaded topical gel. The optimized gel formulation exhibited a homogeneous consistency, with a pH of 6.8 and a viscosity of 1.15 PaS, indicating its suitability for topical application and stability. The in vitro diffusion studies for the topical gel showed drug release of 82.32% in 24 h. The optimized formulation demonstrated significant antipsoriatic activity, as confirmed through cytotoxicity studies conducted on HaCaT cells. Conclusions: On the basis of the findings, it can be concluded that the prepared nanosponge-loaded topical gel formulation presents a promising solution for the effective management of PsA, offering enhanced drug solubility, sustained release, and improved therapeutic potential. [ABSTRACT FROM AUTHOR]