Delivery System Research Articles

Intranasal Route an Alternative Approach for Systemic Drug Delivery: Recent Strategies and Progression

: Intranasal administration has proven to be a viable alternative for local and systemic delivery of varied therapeutic agents. This route has been potentially researched for delivering polar compounds, vaccines, hormones, peptides, proteins, etc. Being non-invasive and painless with a fast onset of action (both local and systemic), intranasal has become an ideal route for medication to children. This route is specifically employed for the delivery of drugs that are unstable in GIT, which gets significantly degraded or metabolized by the first-pass effect. The nasal route's high absorption and permeability profile has led to its exploration as a substitute for parenteral delivery. This paper reviews the feasibility and potentials of intranasal administration, discussing its benefits, drawbacks, market analysis, factors affecting nasal drug delivery system, conventional and novel strategies (polymeric and nano-carrier-based delivery systems) to improve nasal ab-sorption and its clinical management of varied systemic and topical disorders viz. neurodegenerative, pulmonary, microbial, neoplastic, etc.

Nanotechnology: Current Developments, Applications and Patents for Non-invasive Topical Cosmetics and Dermatological Therapeutic Delivery

: Nanotechnology exhibits the advancement in the field of invention, by improving the potency of the formulation through the delivery of inventive solutions. To resolve several limita-tions related to conventional formulations, nanotechnology applications are increasing in the cosmetics and dermatological area. Cosmetic and dermatological preparations are considered a thriving branch of the body care arena and their usage has increased dramatically through the past years. Scientists are designing innovative delivery mechanisms and emerging innovations that are presently being utilized in the development of cosmetics. Inventive nanocarriers such as nio-somes, liposomes, microemulsions, nanoemulsions, solid-lipid nanoparticles, nanospheres, and nanostructured (lipid) carriers have substituted the use of traditional drug delivery. These innova-tive nanocarriers have the convenience of better skin permeation, sustained and controlled drug delivery, precise location, higher stability, and greater incorporated capability. Since the usage of cosmetics has increased, the usual delivery system has been substituted by modern delivery ap-proaches. The introduction of newer advancements and novel drug delivery systems make cos-metics and cosmeceuticals more popular with increased market share. This review article on nan-otechnology employed in cosmetics and dermatology emphasizes the numerous innovative nanocarriers designed for cosmetic and dermatologic drug delivery, their negative and positive aspects, and their toxicity.

Encapsulation of Antarctic krill peptide by polysaccharide-based nanoparticles: Preparation, characterization, evaluation of stability and hypoglycemic activity

The aim of this study was to construct a chitosan quaternary ammonium salt (HTCC)/sodium alginate (SA) nanoparticle delivery system for the encapsulation of Antarctic krill peptide (AKP), with the goal of enhancing its stability and post-digestive hypoglycemic activity. Additionally, the effect of the content and encapsulation sequence of HTCC/SA on the structure and properties of AKP-loaded nanoparticles (AKP-loaded NPs) was investigated. As the content of the outermost wall material (HTCC) increased, the particle size of nanoparticles initially increased and then decreased. Concurrently, the zeta potential showed a trend of increase, ranging from -38.77 to 46.07 mV. When SA was used as the outermost wall material, the nanoparticles exhibited a smaller particle size (240.1 nm) and better dispersibility. Electrostatic interaction and hydrogen bonding were the major forces involved in the formation of AKP-loaded NPs. X-ray diffraction revealed that AKP was successfully encapsulated in an amorphous state. Scanning electron microscopy showed that AKP-loaded NPs had an elliptical or blocky appearance. Moreover, AKP-loaded NPs demonstrated good storage and temperature stability, while nanoparticles with HTCC in the outermost layer (HTCC:SA=2:1) showed good pH and ionic stability. During simulated digestion, AKP-loaded NPs inhibited the release of AKP in gastric fluid. Consequently, the hypoglycemic activity of digested AKP-loaded NPs was remarkably higher than unencapsulated AKP. Notably, the nanoparticles with HTCC in the outermost layer provided superior hypoglycemic activity. In summary, the polysaccharide-based delivery system exhibited great potential to improve the stability and post-digestive hypoglycemic activity of AKP, broadening its applications in the food and pharmaceutical industries.

Naringenin Nanoformulations for Neurodegenerative Diseases.

Glioblastoma (GBM) is a grade-IV astrocytoma, which is the most common and aggressive type of brain tumor, spreads rapidly and has a life-threatening catastrophic effect. GBM mostly occurs in adults with an average survival time of 15 to 18 months, and the overall mortality rate is 5%. Significant invasion and drug resistance activity cause the poor diagnosis of GBM. Naringenin (NRG) is a plant secondary metabolite byproduct of the flavanone subgroup. NRG can cross the blood-brain barrier and deliver drugs into the central nervous system when conjugated with appropriate nanocarriers to overcome the challenges associated with gliomas through naringenin-loaded nanoformulations. Here, we discuss several nanocarriers employed that are as delivery systems, such as polymeric nanoparticles, micelles, liposomes, solid lipid nanoparticles (SLNs), nanosuspensions, and nanoemulsions. These naringenin-loaded nanoformulations have been tested in various in vitro and in vivo models as a potential treatment for brain disorders. This review nanoformulations of NRG can a possible therapeutic alternative for the treatment of neurological diseases are discussed.

A Critical Appraisal of Functionalized 2-Dimensional Carbon-Based Nanomaterials for Drug Delivery Applications.

The development of an efficient and innovative drug delivery system is essential to improve the pharmacological parameters of the medicinal compound or drug. The technique or manner used to improve the pharmacological parameters plays a crucial role in the delivery system. In the current scenario, various drug delivery systems are available where nanotechnology has firmly established itself in the field of drug delivery. One of the most prevalent elements is carbon with its allotropic modifications such as graphene-based nanomaterials, carbon nanotubes, carbon dots, and carbon fullerenes, these nanomaterials offer notable physiochemical and biochemical properties for the delivery applications due to their smaller size, surface area, and ability to interact with the cells or tissues. The exceptional physicochemical properties of carbon-based 2D nanomaterials, such as graphene and carbon nanotubes, make them attractive candidates for drug delivery systems. These nanomaterials offer a large surface area, high drug loading capacity, and tunable surface chemistry, enabling efficient encapsulation, controlled release, and targeted delivery of therapeutic agents. These properties of the nanomaterials can be exploited for drug delivery applications, like assisting the target delivery of drugs and aiding combination molecular imaging. This review emphasizes on the recent patents on 2D carbon-based nanomaterial and their role in drug delivery systems. Carbon-based 2D nanomaterials present a wealth of opportunities for advanced drug delivery systems. Their exceptional properties and versatility offers great potential in improving therapeutic efficacy, minimizing side effects, and enabling personalized medicine and the recent patents on 2D nanomaterial.

Dextran-based Drug Delivery Approaches for Lung Diseases: A Review.

Respiratory disorders, such as tuberculosis, cystic fibrosis, chronic obstructive pulmonary disease, asthma, lung cancer, and pulmonary inflammation, are among the most prevalent ailments in today's world. Dextran, an exopolysaccharide formed by Leuconostoc mesenteroides (slimeproducing bacteria), and its derivatives are investigated for several therapeutic utilities. Dextranbased drug delivery system can become an innovative strategy in the treatment of several respiratory ailments as it offers numerous advantages, such as mucolytic action, airway hydration, antiinflammatory properties, and radioprotective effect as compared to other polysaccharides. Being biocompatible, flexible hydrophilic nature, biodegradable, tasteless, odourless, non-mutagenic, watersoluble and non-toxic edible polymer, dextran-based drug delivery systems have been explored for a wide range of therapeutic applications, especially in lungs and respiratory diseases. The present article comprehensively discusses various derivatives of dextran with their attributes to be considered for drug delivery and extensive therapeutic benefits, with a special emphasis on the armamentarium of dextran-based formulations for the treatment of respiratory disorders and associated pathological conditions. The information provided will act as a platform for formulation scientists as important considerations in designing therapeutic approaches for lung and respiratory diseases. With an emphasis on lung illnesses, this article will offer an in-depth understanding of dextran-based delivery systems in respiratory illnesses.

Preparation of a thermosensitive and antibacterial in situ gel using poloxamer-quaternized chitosan for sustained ocular delivery of Levofloxacin hydrochloride

In this study, a thermosensitive in situ gel with porous structure was developed using poloxamer (Po) and N-(2-hydroxy-3-trimethyl ammonium) propyl chitosan chloride (HTCC). The poloxamer-quaternized chitosan (Po-HTCC) in situ gel exhibited superior rheological property, water absorption capacity and antibacterial activity against Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa and Streptococcus pyogenes, making it well-suited for ocular applications. Scanning electron microscope revealed a macroporous architecture with pore sizes ranging from 1 to 2 μm, suggesting that the gel has desirable breathability, corneal adhesion capability, and overall conformability. In vitro drug release assay was conducted with levofloxacin hydrochloride, demonstrating that sustained release over 48 h could be achieved at 34 °C, with approximately 80 % of the drug released within this timeframe. Computational simulations revealed substantial binding affinity between the material and the Escherichia coli outer membrane lipopolysaccharide-associated protein and corneal mucin. The protein showing the strongest binding energy to N-(2-hydroxy-3-trimethyl ammonium) propyl chitosan chloride (HTCC), as calculated by the Molecular Mechanics Generalized Born Surface Area Method (MM-GBSA), was LptD-LptE, with a binding energy of −61.14 ± 4.72 kcal/mol. These results underscore the potential of this system for effective and convenient ocular delivery with sustained drug release.

Plant-derived extracellular vesicles release combined with systemic DOX exhibits synergistic effects in 3D bioprinted triple-negative breast cancer

Triple-negative breast cancer (TNBC) is a highly aggressive subtype of breast cancer, lacking targeted therapeutic options. Hydrogels, particularly gelatin methacrylate (GelMA), have emerged as promising materials for localized drug delivery due to their biocompatibility and tunable properties. This study investigates a dual-delivery system for enhancing the treatment efficacy of triple-negative breast cancer (TNBC) using a combination of extracellular vesicles (EVs) derived from Citrus limon L. and the chemotherapeutic drug doxorubicin (DOX). We fabricated 3D bioprinted GelMA scaffolds to achieve localized and controlled release of EVs and evaluated their synergistic effects with systemic DOX delivery on both primary and metastatic 3D TNBC models.The GelMA scaffolds, especially those with 95 % methacrylation, exhibited higher stiffness, which enhanced their sustained release. Following 48-h incubation, the combination of EVs and DOX significantly increased cytotoxicity in the primary 3D TNBC model, reducing cell viability to approximately 30 % compared to controls. This was notably more effective than treatments with DOX or EVs alone. During the extended 7-day incubation period, the combination treatment continued to show superior efficacy, with persistently high levels of ROS generation and further reduction in cell viability. In a metastatic 3D TNBC model, a significant sensitivity to the combined treatment was observed, which notably inhibited aggregate formation and migration. Importantly, EVs-embedded scaffolds promoted the proliferation of human fibroblasts, highlighting their non-toxic nature, while concurrently inhibiting TNBC cell growth. This approach provides a promising strategy to improve the treatment outcomes of TNBC by exploiting the synergistic effects of local EVs release and systemic chemotherapy.

Marine Polysaccharides for Gene Delivery: Approaches and Prospective

: Polysaccharides from marine sources have been increasingly used in recent research due to their availability, affordability, biocompatibility, and biodegradability. These features make them promising candidates for use in nanotechnology in a wide variety of drug delivery systems, including those for gene therapy, tissue engineering, cancer therapy, wound dressing, biosensors, and water purification. Marine polysaccharides are of particular interest due to their distinct physicochemical and biological properties like chitin, alginate, carrageenan, fucoidan, and chitosan has inspired an array of nanostructures. This article summarizes the history, chemical composition, biological functions, and nanomedical uses of these marine polysaccharides. Marine polysaccharides are the topic of this review due to their potential utility in gene transfer.

Nanostructured Lipid Carrier-Mediated Transdermal Delivery System of Glibenclamide for Gestational Diabetes: Pharmacokinetic and Pharmacodynamic Evaluation.

Gestational diabetes mellitus (GDM) poses significant risks during pregnancy for both mother and fetus. Adherence to oral antidiabetic medications, like glibenclamide (GB), can be challenging, necessitating novel drug delivery methods. Nanostructured lipid carriers (NLC) offer a promising approach by efficiently permeating the skin due to their small size and lipid-based composition. This study aimed to develop and evaluate transdermal patches loaded with glibenclamide NLCs to treat GDM. Glibenclamide NLCs were prepared using hot homogenization with ultrasonication and melt dispersion method. A central composite design was utilized to optimize the formulations. Transdermal patches containing optimized NLCs were developed using HPMC K 100 and Eudragit L polymers. The patches were evaluated for various parameters, and their pharmacokinetic and pharmacodynamic studies were carried out to assess their safety and efficacy. Optimized NLCs efficiently permeated rat skin. Cell viability studies indicated the nontoxicity of the formulations. NLC-loaded transdermal patches (F2 and F7) showed drug release of 1098 μg/cm2 and 1001.83 μg/cm2 in 24 h, with a 2.5-fold higher flux and permeation coefficient than the GB patch. Pharmacokinetic analysis revealed Tmax of 8 and 10 h and Cmax of 7127 ng/ml and 7960 ng/ml for F2 and F7, respectively, ensuring sustained drug action. AUC0-α was 625681 ng/ml·h and 363625 ng/ml·h for F2 and F7, respectively, indicating improved bioavailability. Transdermal patches incorporating NLCs hold promise for enhancing glibenclamide's therapeutic efficacy in GDM treatment. Improved skin permeation, sustained drug release, and enhanced bioavailability make NLC-based transdermal patches a potential alternative with better patient compliance.

A review of exploring the synthesis, properties, and diverse applications of poly lactic acid with a focus on food packaging application.

Polylactic acid (PLA) is an aliphatic polyester, which is primarily synthesized from renewable resources through the polycondensation or ring-opening polymerization of lactic acid (LA)/lactide. LA can be conveniently produced via the fermentation of sugars obtained from renewable sources such as corn and sugar cane. Due to its biodegradable and biocompatible nature, PLA exhibits a vast range of applications. Its advantages include non-toxicity, environmental safety, and compatibility with human biological systems. PLA finds significant use in various biomedical applications, including implants, tissue engineering, sutures, and drug delivery systems. Additionally, PLA serves as a renewable and biodegradable polymer of extensive utility in film production, offering an alternative to petrochemical-based polymers. Moreover, the properties of PLA-based films can be tailored by incorporating extracts, polysaccharides, proteins, and nano-particles. This review encompasses LA production, PLA synthesis, and diverse applications of PLA and further explores the potential of PLA in the realm of packaging.

Engineered biomimetic nanovesicles-laden multifunctional hydrogel enhances targeted therapy of diabetic wound

Angiogenesis is essential for diabetic wound healing. Endothelial progenitor cell-derived extracellular vesicles (EPC-EVs) are known to promote wound healing by enhancing angiogenesis, while the low yield and lack of effective targeting strategies limit their therapeutic efficacy. Here, the biomimetic nanovesicles (NVs) prepared from EPC (EPC-NV) through an extrusion approach were reported, which functioned as EV mimetics to deliver contents from EPC to the wound. Besides, the cRGD peptide was coupled to the surface of EPC-NV (mEPC-NV) to achieve active endothelial cells (ECs)-targeting. Furthermore, we developed a dual hydrogel network by combining Fe3+@ Protocatechualdehyde (PA) complex-modified Acellular Dermal Matrix (ADM) with light-cured gelatin (GelMA), to enrich and sustainably release mEPC-NV. The hydrogel system with antioxidant and antibacterial properties also made up for the deficiency of mEPC-NV, reducing reactive oxygen species (ROS) and inhibiting infection in diabetic wound. Taken together, this study established a novel bioactive delivery system with angiogenesis, antioxidant and antibacterial activities, which might be a promising strategy for the treatment of diabetic wound.

Preparation, Characterization, and Evaluation of Mesoporous Silica Nanoparticles in Enhancing Oral Bioavailability of Poorly Water-Soluble Drugs.

Breviscapine (BVP) is one of the extracts of several flavonoids of Erigeron breviscapus, which has been widely used in the treatment of cerebral infarction and its sequelae, cerebral thrombus, coronary heart disease, and angina pectoris. But BVP has poor solubility. The objective of the study is to develop mesoporous silica nanoparticles (MSNs) that can be loaded with a drug with poor water solubility. The MSNs, which were designed for oral administration, enhanced both the dissolution rate and drug loading capacity. The use of MSNs as an oral drug delivery system was investigated by SEM, TEM, BETBJH, XRD, FT-IR, and HPLC. Additionally, we examined the oral bioavailability of BVP loaded onto MSNs and examined the cellular cytotoxicity of MSNs. The results indicate that the oral bioavailability of BVP after loading onto MSNs was greater than that of a marketed product. Furthermore, we studied the mechanism by which MSNs enhance the oral absorption of BVP. MSNs have the potential to enhance the oral bioavailability of poorly water-soluble drugs by accelerating the drug dissolution rate.

Gelatin microcarriers as an effective adipose-derived stem cells delivery strategy in osteoarthritis treatment

Despite their clinical success, stem cells (SCs) in the treatment of osteoarthritis (OA) are limited by lower retention efficiency and restricted paracrine function. The development of effective SCs culture and delivery systems to maintain or promote SCs paracrine function is urgently needed. In this study, we focused on gelatin microcarriers with different sizes as SCs culture scaffold for OA therapy. The effect of culturing adipose-derived stem cells (ADSCs) on different size microcarriers (180 μm and 320 μm) to promote paracrine function was evaluated. The secretome of ADSCs cultured on microcarriers more effectively regulated macrophages and chondrocytes in a direction favorable to OA healing compared to culture plates. In particular, microcarriers with ADSCs effectively reduced the coefficient of friction at the cartilage interface. Injection low-dose ADSCs without and with different size microcarriers into the knee joints in rats' OA model was achieved. Even better OA therapeutic effects were achieved by using smaller size (higher curvature) microcarriers to deliver ADSCs at low doses. Microcarrier-based cell delivery strategies offer potential solution method for OA therapy.

Coupling simulation and experimental study of drug loading and releasing behaviors in phytol-based micelles

Phytol, as a potential drug-carrier, can regulate the cellular reactive oxygen species (ROS) levels in a dose-dependent manner, decreasing them at lower doses and increasing them at higher doses. In this study, we developed phytol-based micelles composed of phytol, PEG, and OE, which can clearly enhance drug delivery efficacy and simultaneously protect normal cells. Drug-loading and -releasing mechanisms of phytol-based micelles were investigated combined with dissipative particle dynamics (DPD) simulations and experimental. The simulation results indicate that Ph4EO22Ph4 exhibits the most desirable properties for forming phytol-based micelles compared with other phytol-based polymers we designed. We found that co-loading (purpurin 18 a) P18 and paclitaxel (PTX) within the Ph4EO22Ph4 micelle not only enhances the encapsulation efficiency (EE) of P18 (P18’s EE rised from 85.16 % to 91.17 %) but also optimizes the overall micellar structure, exhibiting excellent DL capability along with sustained release (75.2 % PTX releasing after 72 h) performance under acidic conditions. The release mechanism varies with the loaded drugs, in which PTX is released in its molecular form while P18 is released through P18/Ph4 particles. In the latter case, Ph4 within the particles significantly facilitates cellular uptake of P18 drugs by 4T1 cells, thereby enhancing therapeutic efficacy. Interestingly, Ph4EO22Ph4 exhibited significantly higher cytotoxicity towards 4T1 cells compared to HC11. Therefore, the phytol-based micelles incorporating a concentration-dependent hydrophobic block and a steric effect-driven hydrophilic block composed of PEG demonstrated enhanced efficacy and reduced toxicity. The present study presents a novel phytol-based micelle system incorporating DPD simulation and experimental validation, which effectively addresses the challenges encountered by P18 and PTX. Moreover, it comprehensively investigates drug loading and releasing behaviors in phytol-based micelles from various perspectives, thereby offering valuable insights for the design of alternative drug delivery systems.

Self-assembled sustainable bionanocomposite hydrogels from chitosan for the combination chemotherapy of hydrophobic and hydrophilic drugs.

Self-assembled hydrogels derived from naturally sourced polymers have gained significant interest in drug delivery applications, owing to their potential, exceptional biocompatibility and sustainable properties. This work presents the development and application of self-assembled nanocomposite hydrogels from chitosan and nanosilver as a pH responsive drug delivery system for the controlled release of doxorubicin and paclitaxel in anticancer therapy. Chitosan was functionalized with 4-formyl benzoic acid for incorporating both hydrophobic and hydrophilic anticancer drugs. The self-assembled nanocomposite hydrogels formed from chitosan and 4-formyl benzoic acid by various non-covalent interactions were studied by FT-IR, Dynamic Light Scattering (DLS), and rheology analysis. Rheology studies demonstrated the hydrogel's shear-thinning nature, enabling easy injection. The antibacterial activity can be evidenced by agar-well diffusion assay and MIC values were measured. The antibacterial effect was analyzed by agar-well diffusion assays and H2-DCFDA assay, providing a comprehensive understanding. In-vivo pharmacokinetic studies on Wistar rats demonstrated promising and effective systemic circulation of drug loaded material in blood, thus supporting its potential for therapeutic applications. All these studies and results demonstrates feasibility and a novel synergistic dual drug delivery approach, promising the synergy between hydrophobic paclitaxel (PTX) and hydrophilic Doxorubicin hydrochloride (Dox.HCl), for improved anticancer efficacy.

Emerging Nanotechnology-based Therapeutics: A New Insight into Promising Drug Delivery System for Lung Cancer Therapy.

Lung cancer is a foremost global health issue due to its poor diagnosis. The advancement of novel drug delivery systems and medical devices will aid its therapy. In this review, the authors thoroughly introduce the ideas and methods for improving nanomedicine- based approaches for lung cancer therapy. This article provides mechanistic insight into various novel drug delivery systems (DDSs) including nanoparticles, solid lipid nanoparticles, liposomes, dendrimers, niosomes, and nanoemulsions for lung cancer therapy with recent research work. This review provides insights into various patents published for lung cancer therapy based on nanomedicine. This review also highlights the current status of approved and clinically tested nanoformulations for their treatment. For finding scholarly related data for the literature search, many search engines were employed including PubMed, Science Direct, Google, Scihub, Google Scholar, Research Gate, Web of Sciences, and several others. Various keywords and phrases were used for the search such as "nanoparticles", "solid lipid nanoparticles", "liposomes", "dendrimers", "niosomes", "nanoemulsions", "lung cancer", "nanomedicine", "nanomaterial", "nanotechnology", "in vivo" and "in vitro". The most innovative and cutting-edge nanotechnology-based approaches that are employed in pre-clinical and clinical studies to address problems associated with lung cancer therapies are also mentioned in future prospects. A variety of problems encountered with current lung cancer therapy techniques that frequently led to inadequate therapeutic success are also discussed in the end. The development of nanoformulations at the pilot scale still faces some difficulties, but their prospects for treating lung cancer appear to be promising in the future. Future developments and trends are anticipated as the evaluation comes to a close.

Supersaturated drug delivery system of albendazole salt-polymer complex for improving oral bioavailability and efficacy anti-secondary E. multilocularis

Based on the supersaturation theory, this study devised two albendazole (ABZ) salt-polymer complexes that enhance the oral bioavailability and efficacy of secondary hepatic alveolar echinococcosis (HAE) in rats. Solid characteristics, microstructure, and stability of ABZ benzenesulfonate (ABZ-BSA) and ABZ methanesulfonate (ABZ-MSA) were evaluated. The equilibrium solubility and intrinsic dissolution rate of salt were measured across different pH environments to determine its potential for generating supersaturation. Polymer crystallization inhibitors were subsequently introduced to assess their impact on sustaining supersaturation. The pharmacokinetics and anti-echinococcosis effects of ABZ were evaluated in healthy SD and HAE rats. The characteristic peaks corresponding to amino acid esters and benzimidazole in the ABZ salt structure either shifted or disappeared, corroborated by PXRD, signifying successful ABZ salt preparation. Furthermore, reductions in the melting point and enthalpy of the salts were observed, along with discernible differences in microstructure compared to ABZ. The drug salts exhibited a significant increase in apparent solubility and intrinsic dissolution rate of ABZ, thus laying the groundwork for supersaturation. Stability assessments indicated that salts were susceptible to moisture absorption, necessitating stringent humidity control measures. Notably, HPMC-AS demonstrated promising capabilities in sustaining supersaturation. Finally, pharmacokinetic analyses revealed a substantial increase in the AUC of ABZ-BSA-H and ABZ-MSA-H by 7.6 and 20.3 times, respectively, compared to ABZ in vivo. After a 30-day once-daily oral administration of the Salts and ABZ to SD rats with hepatic alveolar echinococcosis, the ABZ-BSA-H and ABZ-MSA-H formulation demonstrated a cysts inhibition effect 9.2-fold and 15.3-fold greater than that of ABZ. The salt-HPMC-AS complex could potentially be developed into an improved anti-AE drug therapy. Therefore, the salt-HPMC-AS complex could be developed into an enhanced anti-AE drug therapy.

Enhanced brain delivery and antiproliferative activity of resveratrol using milk-derived exosomes

The polyphenol resveratrol (RSV) undergoes extensive phase II metabolism, which limits its bioavailability and bioactivity, including anticancer effects. Growing preclinical evidence reinforces milk-derived exosomes (EXOs) as promising nanocarrier drugs and bioactives delivery systems. Herein, to overcome the mentioned RSV’s drawbacks, EXOs were loaded with RSV (EXO-RSV) to evaluate its brain delivery in Sprague-Dawley rats and its in vitro antiproliferative effects against human neuroblastoma SH-SY5Y and glioblastoma U-87MG cancer cells compared with non-encapsulated RSV. Pharmacokinetic analyses in perfused brains showed RSV detection only after EXO-RSV administration, not after non-encapsulated RSV administration. Encapsulation also resulted in lower concentrations of phase II-derived RSV metabolites in circulation. Additionally, blood-brain barrier (BBB) transport assays using human brain microvascular endothelial cells (HBMECs) corroborated that encapsulation enhanced RSV transport efficiency and protected it from cellular metabolism. In vitro and in silico analyses of phase-II conjugates, primarily RSV 3-glucuronide, showed lower capacity than RSV to cross the BBB. Finally, EXO-RSV (47−750 nM) showed an increased dose-dependent antiproliferative efficacy on both cancer cell lines compared with the non-encapsulated RSV (10 μM), which was ineffective after 72 h of treatment. Our findings suggest that EXOs protect RSV from phase II metabolism and enhance its brain delivery and antiproliferative activity.

Synthesis, modification, characterization, and in vitro evaluation of chitosan-hyaluronic acid coated MIL-100 (Fe) nanoparticles for methotrexate delivery in rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by inflammation of the joints, leading to pain, swelling, and potential joint destruction. Effective management of RA is crucial to improve patients' quality of life and prevent long-term disability. Methotrexate (MTX) is a widely used disease-modifying antirheumatic drug (DMARD) that has shown efficacy in treating RA. However, its use is often limited by significant adverse effects, particularly on healthy tissues and organs, including hepatotoxicity, myelosuppression, and gastrointestinal complications. Therefore, developing targeted drug delivery systems (DDSs) for MTX is essential to enhance its therapeutic effects while minimizing systemic toxicity. Metal-organic frameworks (MOFs), specifically MIL-100(Fe), present a promising approach for targeted drug delivery in RA treatment due to their high porosity, large surface area, and excellent loading capacity. The acid-responsive properties of MIL-100(Fe) make it particularly suitable for targeting the acidic microenvironment of inflamed joints. In this study, we synthesized MIL-100(Fe) using a microwave-assisted method and embedded MTX within these nanocarriers. The nanocarriers were subsequently coated with chitosan and modified with hyaluronic acid through 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC). Comprehensive characterization techniques such as dynamic light scattering (DLS), zeta potential analysis, Brunauer-Emmett-Teller (BET) surface area measurement, X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FT-IR), and field emission scanning electron microscopy (FESEM) were employed to evaluate the nanoparticles. Additionally, we assessed cell cytotoxicity and cellular uptake in macrophage cell lines. Overall, the results indicate that the prepared MIL-100(Fe) nanoparticles are a suitable DDS for targeted MTX delivery in RA treatment.