BACKGROUND:Idiopathic pulmonary fibrosis (IPF), a potentially fatal illness, significantly alters normal lung structure and function, resulting in severe respiratory failure and death. As of yet, no curable remedy has been revealed. Nebivolol is a third-generation β-blocker that has numerous cytoprotective properties and is used to treat heart failure and hypertension. Its potential ability to prevent bleomycin-induced IPF has not been studied. The aim of the current study is to investigate the antifibrotic effect of nebivolol against bleomycin-induced lung fibrosis. METHODS:Twenty-four male Wistar rats were randomly divided into four groups (n = 6 per group): control, bleomycin, nebivolol, and nebivolol + bleomycin. Pulmonary fibrosis was induced by bleomycin administration, while nebivolol was given seven days prior to a single intratracheal injection of bleomycin, daily orally for 21 days. At the end of the study, lung injury and fibrosis were evaluated using histopathological analysis, lung wet/dry ratio, bronchoalveolar lavage fluid protein content, oxidative stress markers, inflammatory cytokines, and fibrosis-related signaling. RESULTS:Nebivolol significantly decreased the histopathological injuries demonstrated through lung tissue sections stained by hematoxylin/eosin and silver. It considerably decreased the lung wet/dry ratio, as well as the total protein level in bronchoalveolar lavage fluid. Further, nebivolol restored superoxide dismutase activity and suppressed elevated malondialdehyde levels, rebalancing the disrupted oxidative indicators. Nebivolol is additionally known to have anti-inflammatory effects, as demonstrated by a decrease in cytokine levels, including tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and interleukin-6 (IL-6), while boosting the secretion of the anti-inflammatory mediator endothelial nitric oxide synthase. In addition, nebivolol's anti-inflammatory properties were obvious by its suppressing effect on Toll-like receptor 4 (TLR4) level and the matrix metalloproteinase-2 (MMP-2) expression. Finally, nebivolol mitigated the progression of the fibrotic cascade, as indicated by reducing the elevated levels of transforming growth factor beta (TGF-β) and heat shock protein 47 (HSP47). CONCLUSION:Nebivolol treatment exhibited remarkable protective effects on bleomycin-mediated IPF in rats via suppressing TLR4/IL-1β/MMP-2 and TGF-β/HSP47 signaling pathways. This study might provide an innovative therapeutic approach to prevent the devastating lung scarring associated with IPF.

The objective of the current investigation was to develop a novel clobetasol propionate (CP) emulgel to enhance the efficacy and minimize side effects during topical application. Preparation of CP loaded emulsion was carried out by the hot emulsification method. The emulsion consisted of combinations of surfactants (Span 20/Tween 20), cosolvent (polyethylene glycol 400), preservatives (methylparaben, propylparaben), with liquid paraffin as the oil phase. The selected emulsion (batch CP7) has nano-size (387.6 ± 58.49 nm), narrow and uniform particle size distribution (PDI, 0.221), spherical morphology and negative zeta potential (–36.4 ± 5.66 mV). The CP7 emulsion was further converted to emulgel by incorporating it in carbopol 934 (2

Background: Diabetic Foot Ulcers (DFUs), a serious diabetes consequence, are caused primarily by hyperglycemia, oxidative stress, and chronic inflammation. This study aims to evaluate the therapeutic potential of liposome-based formulations containing curcumin, colostrum, or both for oral and topical delivery in DFU management. Materials and Methods: The thin film hydration approach was used to develop the liposomes, and their pharmaceutical characteristics were assessed. These liposomes were modified into hydrogels. Efficacy was evaluated in diabetic rats by measuring blood glucose, body weight, antioxidant status (SOD, CAT, GSH, MDA), HbA1c, insulin, TNF-alpha levels, wound contraction, histopathology, and TNF-alpha protein expression. Results: Liposome-loaded hydrogels were pH-compatible and rheologically suitable for topical use. Glycemic control was significantly improved (p<0.0001) with the colostrum-curcumin combination in oral and topical therapy. A highly significant improvement in antioxidant levels (p<0.0001) was noticed in both oral and topical administration of curcumin and colostrum combination, compared to the positive control group. In addition, the combination reduced the TNF-alpha levels considerably in oral (64.3%) and topical (77.1%). Higher wound contraction, rapid re-epithelialization, and collagen deposition were also observed with the combination. Conclusion: In conclusion the developed curcumin-colostrum-loaded liposomes showed a synergistic effect and could be a novel delivery platform for DFU therapy.

Thiazole derivatives constitute an important structural motif in several anticancer agents, exhibiting diverse enzyme inhibitory mechanisms, including tyrosine kinase inhibition. The epidermal growth factor receptor (EGFR), which is overexpressed in many cancer types, particularly breast cancer, plays a pivotal role in tumor proliferation; thus, its regulation is crucial for controlling cancer cell growth. In this context, the present study focuses on the design and synthesis of cost-effective thiazole-based analogues with potential anticancer activity. A new series of imidazo[2,1-b]thiazole derivatives 6a-6j was synthesized via multistep condensation reactions under mild conditions using substituted phenacyl bromides and 2-aminothiazoles. The synthesized compounds were thoroughly characterized by 1H-, 13C-, and 19F-NMR spectroscopy, high-resolution mass spectrometry (HRMS), and single-crystal X-ray diffraction (XRD) analysis. Single-crystal XRD analysis of compound 6b revealed a planar molecular structure stabilized by significant intramolecular hydrogen bonding interactions with supramolecular assembly governed by intermolecular chalcogen and hydrogen bonds. These solid-state intermolecular interactions were investigated using Hirshfeld surface (HS), energy framework (EF), molecular electrostatic potential (MEP), non-covalent interactions (NCI) index, and quantum theory of atoms in molecules (QTAIM) studies. All synthesized derivatives were evaluated for their in vitro anticancer activity using the standard MTT assay against the MCF-7 breast cancer cell line. Among the tested compounds, derivative 6i exhibited notable cytotoxic activity, surpassing the reference drug cisplatin. Overall, the results highlight the anticancer potential of this novel imidazo[2,1-b]thiazole scaffold, with compound 6i emerging as a promising lead for further development of effective anticancer agents.

Objectives The Acinetobacter baumannii complex (ABC) is a hospital-acquired pathogen that exhibits high resistance, particularly to beta-lactam antibiotics. The rise of beta-lactamase enzymes, including carbapenemases, limits treatment options. New beta-lactam/beta-lactamase inhibitor (BL-BLI) combinations show promise, but information on their use in Indian hospitals is inadequate. The current study was designed to investigate the effectiveness of BL-BLI against ABC isolates, assess the impact of co-harboring various resistance genes on antibiotic effectiveness, and map the distribution pattern of these genes in clinical A. baumannii strains obtained from patients admitted at different wards and units of a tertiary care hospital using cluster analysis.Methods For the study, a total of 155 non-repetitive ABC isolates were isolated from specimens (n=9,753) collected from various critical care units and different inpatient departments of a tertiary care hospital. Antimicrobial susceptibility testing was performed on the isolates using Vitek-2 and Kirby-Bauer disc diffusion methods. Conventional PCR was performed to identify beta-lactamase genes, including blaCTX-M, blaTEM, blaKPC, blaNDM, blaOXA-48, and blaOXA-23. The genetic relationships between ABC and the respective hospital wards from which they were isolated were studied using a dendrogram.Results Among BL-BLI combinations, sulbactam-durlobactam showed the highest effectiveness against blaOXA-23, blaKPC, and blaOXA-48 producing ABCs. However, it had limited activity against blaNDM-positive strains, whether alone or in combination. The PCR results reveal that the most widespread genes were blaOXA-23 (65.1 %) and blaNDM (60 %), respectively.Conclusions The high prevalence of carbapenemase genes in ABC isolates, which underscores the limited effectiveness of newer BL-BLI against NDM-positive strains.

Background: Both rutin and brucine can suppress tumor growth mainly through the induction of apoptosis.This study aims to evaluate the potential of nanosponge based delivery to enhance the therapeutic efficacy of rutin and brucine combination against cancer. Materials and Methods: Rutin and brucine nanosponges were prepared separately by employing the quasi-emulsion solvent diffusion method.The formulations were examined for various pharmaceutical properties as well as antioxidant and cytotoxicity effects. Results: The prepared nanosponges resulted in higher drug encapsulation (81% and 88% for rutin and brucine, respectively). FTIR, DSC, and XRD confirm the successful entrapment of bioactives and amorphous dispersion without drug-excipient interactions. Scanning electron microscopy revealed spherical, non-aggregated particles with size range of 300-400 nm. In vitro release studies demonstrated sustained drug release from nanosponges compared to pure bioactives. The DPPH radical scavenging assay showed that combined delivery of nanosponges produced superior antioxidant activity, displaying a synergetic effect at lower concentrations (10-50 mu g/mL). Notably, cytotoxic effect on HaCaT cell lines showed that the combination of delivery leads to similar to 4 fold improvement in potency with marked reduction in IC50 (20.66 mu g/mL) than individual administration. Conclusion: Combination administration using developed nanosponges led to a notable rise in antioxidant activity as well as enhanced anticancer activity, suggesting that this could be a viable strategy for cancer therapy.

Polymeric nanoparticles are a state-of-the-art innovation in nanomedicine, offering site-specific drug delivery, an improved pharmacokinetic profile, and a reduced systemic toxic profile. These nano systems usually range in size between 10 to 100 nm, and have the ability to trap a wide range of pharmacological agents, releasing them on a timed basis to specific sites related to the disease, which improves clinical outcomes. Other novel applications of nanoparticles have included polymer-metal theranostic nanoparticles, which combine both diagnostic and therapeutic functions into a single platform. Further development of the polymeric nanocarrier to clinical application is however complex because of the complex design variables, lack of batch-to-batch properties, scale effects, as well as regulatory uncertainty, due to the fact that the formulation and optimisation of nanoparticles is a long-term and intricate process, scientists actively use artificial intelligence (AI) and machine learning (ML) to learn more about the pattern of drug release in nanoparticles, optimisation of AI and ML is also being done. These barriers are being overcome more and more by using artificial intelligence (AI) and machine learning (ML) to design and optimise nanoformulations. These tools facilitate the forecasting of nanoparticles' behaviour, speed up formulation development, and optimise the pre-clinical and clinical workflow. The success rate of regulatory approvals of polymeric drug delivery systems is, however, modest despite encouraging pre-clinical outcomes. The downfall of the projects is usually linked to inadequate physicochemical characterisation, safety issues and vague regulatory pathways. However, some formulations have managed to overcome these challenges, albeit with the need for a robust design plan, thorough pre-clinical testing, and initial interaction with regulatory authorities. This review explores the rationale behind the development of polymeric nanoparticles, recent AI-driven advancements, and the unique dual-functional capabilities of polymer–metal theranostics. It also examines the factors influencing success or failure in clinical and regulatory settings. Collectively, these insights emphasise the transformative promise of polymeric nanomedicine and highlight the urgent need for integrated technological and regulatory approaches to expedite clinical translation.

Wound healing is a dynamic and multifaceted biological process involving hemostasis, inflammation, proliferation, and tissue remodeling. Topical therapy is widely preferred for wound management due to its localized action and reduced systemic adverse effects. However, the effective delivery of therapeutic agents is often limited by the skin’s barrier properties, the complex wound microenvironment, and the physicochemical characteristics of drugs. This review highlights the key physicochemical parameters governing topical drug delivery in wound therapy, including drug solubility, molecular size, lipophilicity, vesicle size distribution, surface charge, encapsulation efficiency, lipid composition, ethanol concentration, and vesicle deformability, which collectively influence drug permeation and retention at the wound site. Nanovesicular delivery systems have emerged as promising strategies to overcome these limitations. In particular, ultradeformable vesicles such as ethosomes, transferosomes, and transethosomes have demonstrated enhanced skin permeation and improved drug deposition in periwound tissue due to their flexible membrane structure and optimized physicochemical properties. This review systematically discusses the composition, preparation techniques, and critical formulation parameters of these vesicular systems that determine their stability, elasticity, and permeation performance. Furthermore, their applications in delivering anti-inflammatory drugs, antimicrobial agents, bioactive phytochemicals, and regenerative therapeutics for different wound types are examined. Widely used in vitro, ex vivo, and in vivo evaluation methods, including permeation studies and wound healing models such as excision, burn, infected, and diabetic wounds, are also summarized. Finally, the review outlines current challenges related to formulation standardization, physicochemical characterization, safety assessment, and large-scale production, while highlighting the future potential of ultradeformable vesicles as next-generation nanocarriers for advanced wound healing therapies.

The low water solubility of numerous drug candidates and phytochemicals continues to pose a significant challenge in pharmaceutical development, greatly limiting their bioavailability and therapeutic performance. This review presents a detailed overview of formulation strategies aimed at improving the solubility and dissolution of poorly aqueous-soluble compounds. The biopharmaceutics classification system and the relevance of in vitro-in vivo correlation, as well as key challenges in formulation development, are briefed. Solid-state and particle engineering approaches, including micronization, supercritical fluid technology, electrospinning, and cryogenic techniques, are discussed. Extensive critical examination of amorphous solid dispersions and their preparation methods, as well as crystallization inhibition strategies, is covered. Cocrystallization is highlighted as a promising approach, with emphasis on design principles and preparation methods. Various solubilization techniques, such as pH modification, cosolvency, hydrotropy, micellar solubilization, and cyclodextrin-based complexation, including advanced hybrid systems, are also explored. Emerging solvent platforms, such as deep eutectic systems and lipid-based and nanotechnology-driven approaches, are reviewed for their role in improving solubility and drug delivery. Additionally, enabling technologies such as liquisolid systems and hydrophilic polymers are addressed. Despite notable progress, limitations such as scalability, reproducibility, regulatory constraints, and long-term safety persist. Overall, this review provides integrated insights into formulation design approaches to enhance the solubility and therapeutic efficacy of poorly soluble drugs.

The therapeutic efficacy of ellagic acid could be improved by developing suitable carrier system. The present research was to develop ellagic acid-loaded microsponges impregnated with chitosan-guar gum hydrogel and evaluate its potential as novel carrier system for wound therapy. Ellagic acid-loaded microsponges were fabricated using ethyl cellulose by the quasi-emulsion solvent diffusion method and incorporated into chitosan and guar gum hydrogel. Prepared microsponges were found to be spherical, non-aggregated particles ranging in size from 100 to 300 µm. The hydrogel formulation was assessed for pharmaceutical characteristics, rheology, drug release, antioxidant and antimicrobial activities. FTIR confirmed that the bioactive and the excipients used are chemically compatible. Spreadability data confirm precise and easy dosage application of microsponge hydrogel in the skin. Results of rheological studies revealed that microsponge-loading considerably increased elastic strength, while frequency and temperature sweep tests demonstrated viscoelastic stability at 25°C. A sustained ellagic acid release for 12 h following the Higuchi kinetics model (R2 = 0.987) was noticed with microsponge loaded chitosan-guar gum hydrogel. The good antioxidant activity exhibited at doses (50-100 µg/mL) by the developed hydrogel implies that the formulation successfully preserves bioactive antioxidant properties. Developed hydrogel retained antimicrobial activity against the test organisms and showed notable inhibition against Pseudomonas aeruginosa at low concentration (12.5 µg/mL). This study establishes an effective topical formulation of ellagic acid-loaded microsponges with potential antioxidant and antimicrobial efficacy, highlighting its possibility to be used for wound healing.

Objectives: The present study was designed to repurpose aripiprazole (AR) as an antifungal drug for the management of topical candidiasis using a bioadhesive sponge incorporating a hyaluronic acid (HA)-, ceramide-, and terpene-based vesicular nanosystem (HCT-NS). Methods: AR-loaded HCT-NS were formulated by the modified ethanol injection method with varying amounts of HA, ceramide, and two types of terpenes. The formulation optimization of AR-loaded HCT-NS was carried out by a full factorial design. The responses evaluated were zeta potential (ZP), particle size (PS), and entrapment efficiency (EE). Results: The optimized AR-loaded HCT-NS has 5 mg of HA, 10 mg of ceramide, and fenchone, which showed spherical vesicles with EE of 81.21 ± 0.01%, PS of 223.25 ± 11.25 nm, polydispersity index (PDI) of 0.492 ± 0.003, and ZP of −27.74 ± 0.04 mV. The optimum HCT-NS showed a greater drug release in comparison to the AR suspension. In addition, the selected HCT-NS exhibited good bioadhesive characteristics and stayed stable during storage. Confocal laser scanning microscopy confirmed the penetration of the fluorescently optimized HCT-NS via the skin. Further, the scanning electron microscope image indicates the porous structure of the formed sponge. In vivo evaluations for the optimum HCT-NS sponge showed a good antifungal impact against Candida albicans. The safety of topical treatment was confirmed by histopathological examination. Conclusions: Taken together, the results here suggest that the AR-loaded HCT-NS sponge showed potent antifungal activity against Candida albicans fungal infection.

Nanoemulgels have emerged as a promising hybrid drug delivery system that integrates the advantages of nanoemulsions and gels, offering enhanced drug penetration, prolonged residence time, and improved patient compliance. This review provides a comprehensive overview of the therapeutic applications of nanoemulgels in wound healing, microbial infections, skin cancer, and various dermatological disorders. The article begins with an overview of skin architecture and its implications for cutaneous drug delivery, followed by a clear distinction between transdermal and topical drug delivery systems. The mechanisms of drug transport into and through the skin are discussed in detail, highlighting the role of nano-sized carriers, particularly nanoemulsions, in overcoming the stratum corneum barrier. Mechanistic insights into nanocarrier-mediated cutaneous drug transport and their versatility as dermal delivery platforms are described. The formulation aspects of nanoemulgels, including their components and both high-energy and low-energy methods for nanoemulsion preparation, are critically discussed to elucidate their impact on formulation performance. An overview of in vitro characterization techniques and biological screening methods employed to evaluate nanoemulgel performance is presented, along with a tabulated compilation of relevant patents to highlight translational progress. Finally, current challenges, regulatory considerations, and future perspectives are discussed, underscoring the potential of nanoemulgels as a versatile and effective platform for advanced topical drug delivery.

Despite advancements in healthcare settings in developed countries, the early detection and higher mortality rate associated with amyotrophic lateral sclerosis (ALS), a fatal motor neuronal disorder, remain challenging. Recently, quantum dots (QDs) have emerged as a promising nanocarrier in the prognosis and treatment of ALS owing to their unique multifunctional properties. QDs, through their photoluminescence properties upon excitation, can facilitate the identification and real-time monitoring of disease biomarkers. They also act as a nanocarrier for the targeted delivery of therapeutics, avoiding accumulation at the non-targeted sites and minimising toxicity. QDs can be fabricated to conjugate with protein biomarkers linked to ALS, such as specific proteins, nucleic acids, or genetic variants, for the diagnosis of the disease. Such fabrication could lead to enhanced identification and diagnostic patterns of ALS, thereby contributing to improved therapeutic intervention strategies. Furthermore, these tiny structures could be applied in combined biosensor formats to identify ALS-associated biomarkers in body fluids, which would be a highly sensitive diagnostic system. Subsequently, comprehensive multiomics techniques have demonstrated improved identification of newer protein targets associated with neurological complications. Overall, QDs can be explored as a potential tool to identify biomarkers relevant to ALS, diagnose the disease at its early stages, and track the effectiveness of the treatment. The integration of QD with omic-based strategies and network analysis can potentially catalyse a breakthrough in the management of ALS. Therefore, this review aims to explore the application of QDs in ALS diagnosis and management, advancements in research, clinical trials, and patents.

Background/Objectives: This investigation aims to assess the potential for repurposing nitazoxanide (NIT) as a treatment for COVID-19. NIT was loaded into terpene-enriched chondrosomes (TECs) to assess its anti-hCoV-19 activity through pulmonary delivery. Methods: NIT-TECs were then fabricated utilizing the ethanol injection method. Using a D-optimal design, the effects of factors on entrapment efficiency (EE%), particle size (PS), and zeta potential (ZP) were determined, and the optimal formulation was selected. Results: The optimum TEC exhibited an EE% of 98.87 ± 0.69, a PS of 129.43 ± 5.43 nm, a polydispersity index (PDI) of 0.433 ± 0.022, and a ZP of -25.99 ± 0.99 mV. The optimum TEC was lyophilized to attain a dry powder. Further, the differential scanning calorimetry test confirmed that NIT was transformed from crystalline to amorphous form inside the optimum TEC. In addition, the mucoadhesion test confirmed the ability of the optimum TECs to adhere to pulmonary tissues. Additionally, NIT binding to the active site of SARS-CoV-2 enzymes was investigated using in silico analysis. When compared to NIT, the aerodynamic characteristics of the lyophilized optimum TECs employing the cascade impactor showed superior residence in the lungs. Conclusions: These findings suggest that loading NIT into TECs enhanced its antiviral activity, as indicated by the in vitro cytotoxicity study. Overall, the results point to NIT-loaded TECs as a potentially effective pulmonary delivery system for COVID-19 treatment.

Wound healing is a multifaceted biological process comprising the phases of hemostasis, inflammation, proliferation, and remodeling, all of which require supportive microenvironment for optimal tissue regeneration. Biopolymer-based hydrogels, derived from materials such as cellulose and its derivatives, chitosan, alginate, and hyaluronic acid, have emerged as promising wound dressing materials due to their excellent biocompatibility, biodegradability, moisture-retention capacity, and potential to mimic the native extracellular matrix. The structural characteristics, wound healing functions, and underlying mechanisms of these biopolymers are critically examined and summarized in tabular form. The review further highlights the incorporation of natural and synthetic therapeutic agents, growth factors, stem-cell-derived products, and peptides into biopolymer matrices to enhance therapeutic efficacy. The examined research findings indicate significant increases in fluid intake, moisture retention, antibacterial activity, angiogenesis, collagen deposition, tissue regeneration, and wound healing rates. Translational difficulties, regulatory issues, clinical research, and new patent activity pertaining to advanced wound healing biomaterials are also covered in the review. Despite tremendous improvements, issues still exist in bulk manufacturing, long-term safety, reproducibility, mechanical stability, and clinical validation. Future innovations are anticipated to concentrate on smart, multipurpose, and customized hydrogel systems that can integrate drug delivery, biosensing, and regenerative capabilities while reacting dynamically to wound microenvironments. Overall, biopolymer-based hydrogels are a flexible, rapidly developing platform with significant promise to improve next-generation skin tissue engineering and change the treatment of both acute and chronic wounds.

The tumor microenvironment (TME) has a major role in malignancy and its complex nature can mediate tumor survival, metastasis, immune evasion, and drug resistance. Thus, reprogramming or regulating the immunosuppressive TME has a significant contribution to make in cancer therapy. Targeting TME with nanocarriers (NCs) has been widely used to directly deliver anticancer drugs to control TME, which has revealed auspicious outcomes. TME can be reprogrammed by using a range of NCs to regulate immunosuppressive factors and activate immunostimulatory cells. Moreover, TME can be ameliorated via regulating the redox environment, oxygen content, and pH value of the tumor site. NCs have the capacity to provide site-specific delivery of therapeutic agents, controlled release, enhanced solubility and stability, decreased toxicities, and enhanced pharmacokinetics as well as biodistribution. Numerous NCs have demonstrated their potential by inducing distinct anticancer mechanisms by delivering a range of anticancer drugs in various preclinical studies, including metal NCs, liposomal NCs, solid lipid NCs, micelles, nanoemulsions, polymer-based NCs, dendrimers, nanoclays, nanocrystals, and many more. Some of them have already received US Food and Drug Administration approval, and some have entered different clinical phases. However, there are several challenges in NC-mediated TME targeting, including scale-up of NC-based cancer therapy, rapid clearance of NCs by the mononuclear phagocyte system, and TME heterogeneity. In order to harness the full potential of NCs in tumor treatment, there are several factors that need to be carefully studied, including optimization of drug loading into NCs, NC-associated immunogenicity, and biocompatibility for the successful translation of NC-based anticancer therapies into clinical practice. In this review, a range of NCs and their applications in drug delivery to remodel TME for cancer therapy are extensively discussed. Moreover, findings from numerous preclinical and clinical studies with these NCs are also highlighted.

Natural substances, especially those derived from plants, exhibit a diverse range of therapeutic benefits, such as antioxidant, anti-inflammatory, anticancer, and antimicrobial effects. Nevertheless, their use in clinical settings is frequently impeded by inadequate solubility, limited bioavailability, and instability. Nanovesicular carriers, such as liposomes, niosomes, ethosomes, transferosomes, transethosomes, and cubosomes, have emerged as innovative phytochemical delivery systems to address these limitations. This review highlights recent developments in vesicular nanocarriers for phytochemical delivery, emphasizing preparation techniques, composition, therapeutic applications, and the future potential of these systems. Phytosomes, along with their key advantages and various preparation techniques, are extensively described. Various in vitro and in vivo characterization techniques utilized for evaluating these nanovesicular carriers are summarized. Completed clinical trials and patents granted for nanovesicles encapsulating phytochemicals designed for systemic delivery are tabulated. Phytochemical delivery via vesicular carriers faces challenges such as low stability, limited active loading, scalability issues, and high production costs. Additionally, immune clearance and regulatory hurdles hinder clinical application, requiring improved carrier design and formulation techniques.

Introduction Motor and behavioral impairments associated with Parkinson's disease (PD). The primary factors underlying the development of Parkinson's disease include mitochondrial impairment, increased oxidative stress, and the production of Lewy bodies due to protein misfolding. Antioxidants could help parkinsonism's symptoms get better and postpone neurodegeneration. We investigated the neuroprotective effects of curcumin, quercetin, and their combination in a rotenone-induced parkinsonism model.Methods Rats given rotenone 2 mg/kg/day for 14 days developed PD. Doses were selected based on preliminary work. Oral administrations of curcumin (100, 150, and 200 mg/kg), quercetin (30, 40, and 50 mg/kg), or their combination were administered simultaneously with rotenone and continued for a further 14 days. Histological studies as well as tests for assessment of locomotor activity, rota rod test (muscular coordination), Grid test and Open-field test were performed. on the 28th and 29th days.Results The higher doses of the used drugs; curcumin (200 mg/kg) and quercetin (50 mg/kg) enhanced locomotor activity, motor coordination, and mobility better than the lower doses. Furthermore, theysignicantly raised dopamine levels and helped minimize rotenone's produced neuronal damage.Discussion In this study, against parkinsonism both quercetin and curcumin exhibit neuroprotective properties.Conclusion Curcumin and quercetin used together has more positive results than each medicine taken by itself.

Nanosuspensions (NS), with their submicron particle sizes and unique physicochemical properties, provide a versatile solution for enhancing the administration of medications that are not highly soluble in water or lipids. This review highlights recent advancements, future prospects, and challenges in NS-based drug delivery, particularly for oral, ocular, transdermal, pulmonary, and parenteral routes. The conversion of oral NS into powders, pellets, granules, tablets, and capsules, and their incorporation into film dosage forms to address stability concerns is thoroughly reviewed. This article summarizes key stabilizers, polymers, surfactants, and excipients used in NS formulations, along with ongoing clinical trials and recent patents. Furthermore, a comprehensive analysis of various methods for NS preparation is provided. This article also explores various in vitro and in vivo characterization techniques, as well as scale-down technologies and bottom-up methods for NS preparation. Selected examples of commercial NS drug products are discussed. Rapid advances in the field of NS could resolve issues related to permeability-limited absorption and hepatic first-pass metabolism, offering promise for medications based on proteins and peptides. The evolution of novel stabilizers is essential to overcome the current limitations in NS formulations, enhancing their stability, bioavailability, targeting ability, and safety profile, which ultimately accelerates their clinical application and commercialization.

Background/Objectives: Raynaud’s phenomenon (RP) is characterized by an exaggerated vasoconstrictive response of small blood vessels in the fingers and toes to cold or stress. Oral therapy with tadalafil (TDL), a phosphodiesterase-5 inhibitor, is limited by systemic side effects and reduced patient compliance. This study aimed to develop and evaluate a TDL-loaded nanoemulgel for transdermal delivery as a non-invasive treatment alternative for cold-induced vasoconstriction. Methods: TDL-loaded nanoemulsions were prepared using the aqueous titration method with cinnamon oil as the oil phase and Cremophor RH40 and Transcutol as the surfactant–cosurfactant system. The optimized nanoemulsion was incorporated into a carbopol-based gel to form a nanoemulgel. The formulation was characterized for droplet size, morphology, thermodynamic stability, rheological properties, in vitro drug release, skin permeation, and pharmacokinetic behavior. Infrared thermography was employed to assess in vivo efficacy in cold-induced vasoconstriction models. Results: The optimized TDL nanoemulsion exhibited a spherical morphology, a nanoscale droplet size, and an enhanced transdermal flux. The resulting nanoemulgel displayed suitable physicochemical and rheological properties for topical application, a short lag time (0.7 h), and a high permeability coefficient (Kp = 3.59 × 10−2 cm/h). Thermal imaging showed significant vasodilation comparable to standard 0.2% nitroglycerin ointment. Pharmacokinetic studies indicated improved transdermal absorption with a higher Cmax (2.13 µg/mL), a prolonged half-life (t1/2 = 16.12 h), and an increased AUC0–24 compared to an oral nanosuspension (p < 0.001). Conclusions: The developed TDL nanoemulgel demonstrated effective transdermal delivery and significant potential as a patient-friendly therapeutic approach for Raynaud’s phenomenon, offering an alternative to conventional oral therapy.