LITERATURE SEARCH:A non‑systematic search in PubMed, Scopus, and Google Scholar was conducted using relevant terms.
AIM:To develop an in situ gelling buccal spray to improve the permeation and stability of reduced glutathione through the buccal mucosa without using ascorbic acid as an antioxidant. MATERIALS AND METHODS:Glutathione, a hydrophilic thiol peptide classified as a Biopharmaceutics Classification System (BCS) class III drug, exhibits poor oral bioavailability due to limited permeability, enzymatic degradation by gamma-glutamyl transferase, and instability in aqueous environments. The formulation was optimized based on gelling time and glutathione stability and evaluated for spray pattern, in situ gelling time, volume expansion, gel rheology, gel degradation, pH, drug content, in vitro buccal mucosa permeation, and stability. RESULTS:The optimized formulation was transparent and formed an in situ gel within 2-6 min. Liquid chromatography-mass spectrometry (LC-MS) analysis confirmed approximately 98% drug content per 0.2 mL actuation and demonstrated improved stability at 4°C compared with the plain drug solution. In vitro permeation studies showed an approximately 10-fold increase in permeability flux, while stability studies confirmed enhanced stability for more than 1 month under refrigerated conditions. CONCLUSION:The developed in situ gelling buccal spray significantly improved the stability and buccal permeation of reduced glutathione, demonstrating its potential as an effective noninvasive delivery system.
AIM:The isolation efficiency of extracellular vesicles (EVs) is essential to ensure their purity and biological properties. Ultracentrifugation is a traditional method which utilizes high centrifugal forces to separate EVs based on their density. The polyethylene glycol (PEG)-based precipitation method is a scalable and cost-efficient alternative to ultracentrifugation. In this study, two popular techniques used for the isolation of EVs from umbilical cord tissue-derived mesenchymal stem cells (UCT-MSCs): ultracentrifugation and polyethylene glycol PEG-based precipitation methods are examined. MATERIALS AND METHODS:The UCT-MSCs were cultured in a xeno-free environment using human platelet lysate (hPL) to avoid the risk of xenogenic contamination. The MSCs and EVs were characterized to confirm their physical and functional properties. Cytotoxicity was analyzed in both normal and cancer cells, and the cell migration assay was conducted on cancer cells treated with the EVs to examine the biocompatibility and migratory effects. RESULTS AND CONCLUSIONS:The similarity in physical, molecular, and functional characterization of UC-EVs and PEG-EVs suggests that PEG-based precipitation maintained the integrity and biological properties of EVs. Overall, the PEG-based precipitation method for EVs isolation is safe and efficient, making them suitable for regeneration and cancer research.
Exosomes are naturally occurring extracellular vesicles that have emerged as promising bio-inspired nanocarriers for the treatment of neurological disorders owing to their intrinsic biocompatibility, low immunogenicity, and ability to cross the blood-brain barrier. This review highlights recent advances in exosome biology, cargo-sorting mechanisms, and engineering strategies designed to enhance therapeutic delivery and targeting within the central nervous system. Particular emphasis is placed on the application of engineered exosomes in neurodegenerative diseases, stroke, spinal cord injury, neuropathic pain, and neuroinflammatory disorders. In addition, we discuss how exosomes compare with conventional delivery platforms and critically examine the major barriers limiting their clinical translation, including heterogeneity, scalability, reproducibility, purity, and regulatory standardization. By integrating mechanistic insights with translational perspectives, this review provides a framework for the rational design and future clinical implementation of exosome-based nanomedicines for neurological disorders. Relevant literature was identified through searches of PubMed, Scopus, Web of Science, and Google Scholar. Publications available from database inception through [Month Year] were screened using combinations of keywords including "exosomes," "extracellular vesicles," "neurological disorders," "brain-targeted delivery," "exosome engineering," "drug delivery," and "clinical trials." Additional relevant articles were identified through manual searches of reference lists from selected studies and recent reviews.
AIMS:Rheumatoid arthritis (RA) is a chronic inflammatory disorder associated with progressive joint damage and pain. The present study aimed to develop and optimize a capsaicin - diclofenac-loaded nanoemulgel incorporating clove and olive oil for enhanced topical delivery and therapeutic efficacy in RA management. MATERIALS AND METHODS:Central composite design was employed to optimize nanoemulsion composition using oil (5-10%) and Smix (15-20%) as independent variables. The optimized formulation was characterized for particle size, polydispersity index (PDI), zeta potential, transmittance, morphology, rheology, antioxidant activity, cytotoxicity, cell viability, and skin permeation behavior. RESULTS:Optimized formulation exhibited particle size below 200 nm, PDI below 0.3, zeta potential below -10 mV, and transmittance of 92.6%, indicating good stability. Microscopic studies confirmed spherical globules. The nanoemulgel showed skin-compatible pH and non-Newtonian rheological behavior. Enhanced in vitro permeation, deeper skin penetration, and superior antioxidant activity (76.80 ± 2.90%) were observed compared to the conventional suspension. The formulation also demonstrated higher cytotoxicity against inflammatory U937 macrophage-like cells (58.2% at 50 μg/mL), lower IC50 (28.8 μg/mL), and improved MG-63 cell viability (85.8%). CONCLUSIONS:The developed nanoemulgel demonstrated improved physicochemical characteristics, enhanced skin permeation, and promising anti-inflammatory potential, suggesting its suitability as an effective topical delivery system for rheumatoid arthritis management.
INTRODUCTION:Nanoparticle-based drug delivery has emerged as a transformative approach in modern therapeutics, offering improved targeting efficiency, enhanced pharmacokinetics, and reduced systemic toxicity compared to conventional drug delivery systems. AREAS COVERED:This review comprehensively examines major nanocarrier platforms, including lipid-based, polymeric, inorganic, and hybrid systems, with emphasis on their structural design and functional properties. It further explores current advancements in targeting strategies, including passive targeting via the enhanced permeability and retention (EPR) effect and active targeting through ligand-receptor interactions involving antibodies, peptides, aptamers, and small molecules. Key biological and technological barriers to clinical translation are also discussed, such as tumor heterogeneity, abnormal vasculature, dense extracellular matrix, immune clearance, and limited cellular uptake. Additionally, emerging stimuli-responsive systems, including pH-, redox-, and enzyme-sensitive nanocarriers, are highlighted for their role in controlled and site-specific drug release. EXPERT OPINION/COMMENTARY:Despite significant progress, the clinical translation of nanomedicine remains constrained by biological complexities and scalability challenges. Future advancements integrating biomimetic strategies, multifunctional design, and artificial intelligence-driven modeling are expected to enhance targeting precision, biocompatibility, and translational success.
Breast cancer remains a leading cause of cancer-related morbidity and mortality worldwide, with conventional treatments frequently limited by systemic toxicity, multidrug resistance, and high recurrence rates, particularly in triple-negative and metastatic subtypes. Microneedle (MN)- based drug delivery systems have emerged as a minimally invasive platform that bypasses the stratum corneum to enable targeted transdermal and intradermal delivery of chemotherapeutics, nanocarriers, and immunotherapeutics, with reduced systemic exposure. This review critically examines the design principles, fabrication materials, and functional types of microneedles (MNs) as applied to breast cancer therapy. The integration of MNs with nanocarriers, immunotherapy, and stimuli-responsive materials to improve tumor penetration, remodel the immunosuppressive tumor microenvironment, and amplify anticancer immune responses is discussed, along with key biological, safety, and regulatory challenges relevant to clinical translation. Microneedles offer great promise as a versatile platform to increase the effectiveness and safety of breast cancer therapies.
Flavonoids represent one of the most pharmacologically diverse classes of natural polyphenols, demonstrating broad therapeutic potential in oncology, neurodegeneration, cardiovascular, and metabolic disorders. However, their clinical utility has been limited by intrinsic physicochemical deficiencies, including low aqueous solubility, chemical instability, and extensive first-pass metabolism. Traditional formulation strategies have proven inadequate at overcoming these barriers. Nano-enabled delivery platforms circumvent these limitations through rational nanocarrier design, effectively enhancing dissolution kinetics, protecting labile compounds from degradation, and modulating tissue distribution. This comprehensive review critically examines the current landscape of flavonoid-loaded nanoformulations on the recent advancements (2020-2025), with a particular emphasis on cutaneous delivery (topical/transdermal), elucidating formulation-driven mechanisms of bioavailability enhancement. Furthermore, it critically highlights the growing significance of co-delivery approaches of flavonoids with other therapeutic agents or with each other within advanced nanoplatforms in improving therapeutic benefits or diminishing the drug's adverse effects. Nano-engineered delivery platforms effectively neutralize the bioavailability constraints of flavonoids, unlocking their full pharmacological potential and elevating clinical therapeutic efficacy.
AIMS:Topical delivery for skin cancer treatment is a better alternative for a highly localized tumor and lower severity of adverse effects associated with oral or parental administration of chemotherapeutic drugs. Topical delivery of drugs requires specific formulation properties to successfully penetrate the interior barriers of skin layers. Our previous in vitro study showed that essential oil (EO) from Piper sarmentosum inhibited both A375 (melanoma) and A431 (non-melanoma) cells, but not HFF1 (human fibroblast) cells. This study aimed to formulate a nanoemulsion incorporating EO from Piper sarmentosum for topical treatment of skin cancer. MATERIALS AND METHODS:Hydrophilic-lipophilic balance (HLB) was employed to optimize the nano-formulation conditions. Tween 80 and Span 80 were used to adjust the HLB value, and prepared using ultrasonication. Optimization was performed using Response Surface Methodology (RSM) at varying concentrations of EO (1-10%), surfactant mixture (Smix) (10-20%), and ultrasonic amplitude (20-70%). The three response variables are particle size, polydispersity index (PDI), and zeta potential. RESULTS AND CONCLUSION:Our results revealed an optimal HLB value at 13.83, followed by an optimal formulation comprising 10% EO, 10% Smix, and 33% amplitude yielding 27.69 nm, PDI of 0.245, and -13.1 mV. The optimized nano-formulation exhibited desirable physicochemical characteristics, suggesting its potential suitability for topical delivery.
Bipolar disorder (BD) is a chronic and severe mental disorder with a high risk for recurrence, requiring long-term mood stabilization treatment approaches. The hazards of recurrence in BD include illness progression, decreasing treatment response, chronicity, comorbidity, suicidality, increased health service utilization, and greater direct and indirect economic costs. Treatment nonadherence is one of the most common modifiable deficiencies in the maintenance treatment of BD, which exacerbates the risk of recurrence and unfavorable course and outcome. Aripiprazole is the only dopamine partial agonist that is FDA-approved in a long-acting injectable (LAI) formulation for the maintenance treatment of adults with bipolar I disorder (BD-I), offered as both a once-monthly and bimonthly monohydrate. Herein, we synthesize the results supporting the efficacy, safety, and tolerability of both aripiprazole LAI formulations in BD-I. A narrative search was conducted by an expert opinion in the field, as well as targeted bibliographic searching. Both aripiprazole LAI formulations were established as efficacious in the reduction of manic and mixed episodes in adults with BD-I; however, their efficacy for bipolar depression prevention remains unproven. Aripiprazole LAI is well tolerated and safe, with injection site pain, sedation, weight increase, and akathisia being the most common adverse events.
In vitro dissolution tests are an essential tool in pharmaceutical development. The wide variety of mathematical models available for interpreting the obtained profiles creates ambiguity and difficulty in their selection and application. The objective of this work was to develop a structured decision-support framework for the preselection of mathematical models in drug dissolution and release studies, integrating the initial experimental profile observation with model applicability criteria, physicochemical considerations, release behavior characteristics, interpretability aspects, and statistical evaluation. A review of classical and recent dissolution/release models was conducted, highlighting their constraints. Based on this information, a hierarchical and transparent workflow was designed to guide model selection in a more systematic manner. This workflow was applied to representative systems: hydrogels, polymeric films, modular systems (Dome Matrix), and 3D-printed pills, allowing the reduction of the number of candidate models and guiding the selection toward equations consistent with the observed phenomena. The methodology proved to be versatile and applicable to different release mechanisms. The proposed workflow constitutes a flexible and practical tool that facilitates the selection of mathematical models. It does not replace the researcher's judgment, but rather complements it, promoting a more transparent and reproducible use of mathematical modeling in pharmaceutical development.
AIMS:This study aimed to develop and evaluate a ternary co-encapsulation system based on electrospun poly(vinyl alcohol) (PVA) nanofibers containing Aloe vera extract, methylglyoxal (MGO), and collagen for multifunctional wound-healing applications with controlled therapeutic delivery. MATERIALS AND METHODS:Electrospun nanofibers were characterized by scanning electron microscopy and FTIR spectroscopy. Swelling, degradation, and in vitro release profiles were evaluated under physiological conditions. Release kinetics were analyzed using Korsmeyer-Peppas and Weibull models. Antimicrobial activity against Escherichia coli and Staphylococcus aureus was assessed according to JIS Z 2801. Cytocompatibility was evaluated using human fibroblast cultures following ISO 10993-5 guidelines. RESULTS:The co-encapsulated nanofibers exhibited homogeneous morphology with fiber diameters of 350-500 nm and preserved bioactive agents´ integrity. The system showed a biphasic release profile, with rapid Aloe vera release (~80% within 4 h) followed by sustained MGO and collagen release up to 160 h. Release behavior involved coupled diffusion, polymer relaxation, and partial matrix dissolution. The ternary system demonstrated strong antimicrobial activity, achieving approximately 99.4% inhibition of E. coli, while maintaining excellent cytocompatibility with cell viability above 100%. CONCLUSIONS:The ternary co-encapsulation strategy synergistic antimicrobial and regenerative effects through controlled multi-agent delivery in electrospun PVA wound-dressing platforms.
INTRODUCTION:Drugs are generally classified according to the Biopharmaceutics Classification System (BCS) based on their solubility and intestinal permeability. Group I drugs tend to have higher bioavailability due to their high solubility and permeability. Drugs in group II have low solubility and high permeability, while drugs in group III have high solubility and low permeability. Drugs in group IV have low bioavailability and require various techniques to enhance their delivery due to their low solubility and permeability. AREAS COVERED:Bile acids are commonly known as biological molecules with surfactant capabilities and continue to be underutilized in enhancing the pharmaceutical profile of drugs. Hence, this review will explore some of the common drug delivery methods and will focus on the use of bile acids and various applications of nanotechnology to enhance drug delivery, including lipid nanotechnology, as well as carbon nanotubes and quantum dots. The authors aim to provide more insights into drug delivery research and contribute to the development of novel drug delivery strategies. METHOD:A literature search was conducted using ProQuest and PubMed, covering publications up to 10 years. Older references were included as appropriate.
Glioblastoma multiforme (GBM), due to its complex and highly heterogeneous nature, remains one of the deadliest cancers in the world. However, advances in targeted therapy offer hope for improved GBM treatment through extensive research into receptor-mediated targeting approaches that exploit receptors overexpressed on the surface of GBM cells, including interleukin-13 receptor alpha 2 (IL-13Rα2), transferrin receptor (TfR), receptor tyrosine kinases (RTKs), and integrins. Nanoparticles such as liposomes, lactoferrin-based specialized nanocarriers, and gold nanoparticles functionalized with targeting ligands including Pep-1L, lactoferrin, and RGD peptides, and loaded with anticancer drugs such as temozolomide, gefitinib, and epirubicin, are being explored for targeted GBM therapy. These approaches have demonstrated promising preclinical outcomes, with several formulations in early-phase clinical trials to evaluate safety, pharmacokinetics, and therapeutic efficacy. Certain receptors, including periostin (POSTN) and chondroitin sulfate proteoglycan-4 (CSPG4), involved in tumor invasion, glioma stemness, and therapeutic resistance, remain relatively underexplored, presenting opportunities for further research. Despite these advances, clinical translation remains limited by nanoparticle-associated cytotoxicity and off-target effects. This highlights the need for future research focused on developing biodegradable and biocompatible nanomaterials, along with optimized ligand-guided designs, to improve safety and enhance translational feasibility in glioblastoma therapy. Literature search Methodology: [PubMed and Google Scholar; 2006-2026].
AIMS:This study focused on developing an effective Rheumatoid Arthritis (RA) treatment by creating diacerein-loaded nanoparticles. The goal was to create a more efficient RA treatment with fewer side effects, something conventional treatments fail to achieve. MATERIALS AND METHODS:Using the solvent evaporation technique, the researchers produced nanoparticles and formulated them, which they optimized using DOE (Design of Experiments). They also analyzed their nanoparticle formulations through three methods: particle size, entrapment efficiency, and in vitro drug release. RESULTS:Their results indicate controlled drug release and desirable physical-chemical properties that should lead to greater bioavailability, which is a good thing because it leads to less waste. The in-vitro studies show that when using diacerein delivered through nanoparticles, there will be a greater anti-inflammatory response from chondrocytes than if diacerein were administered alone. CONCLUSIONS:Therefore, this study provides evidence that nanoparticles can be used to treat RA, improving drug effectiveness, decreasing systemic toxicity, and improving patient compliance.
Central nervous system (CNS) disorders pose a major global health challenge, yet therapeutic development is impeded by the difficulty of delivering effective drug concentrations to the brain. Based on a literature search of PubMed, Scopus, and Google Scholar (1990-2025), this review delineates the current landscape of computational modeling techniques addressing CNS drug delivery, emphasizing anatomical barriers and physiological transport mechanisms relevant to major neurological diseases. We categorize approaches spanning the molecular dynamics interactions of drug-blood-brain barrier (BBB) to macroscopic continuum and physiologically based pharmacokinetic (PBPK) models that elucidate systemic distribution and brain exposure. These models are assessed across established delivery routes, such as intranasal and intrathecal administration, and emerging methods, including focused ultrasound-mediated BBB opening and targeted nanoparticle delivery. We highlight the growing importance of integrating complex physiological phenomena, such as glymphatic flow and cerebrospinal fluid (CSF) dynamics, into predictive models. Finally, we explore opportunities involving multiscale digital twins of the CNS that integrate molecular interactions, vascular hemodynamics, perivascular flow, and parenchymal transport within patient-specific geometries. We also examine the role of machine learning and surrogate modeling in accelerating prediction of drug transport parameters and optimizing delivery strategies, aiming to guide the design of robust computational platforms.
AIMS:This study aimed to develop a targeted drug delivery system based on anti-CD22 single-chain variable fragment (ScFv) conjugated to β-cyclodextrin (β-CD) Bio-MOFs for the selective delivery of daunorubicin (DNR) to CD22-positive B-cell tumor cells. MATERIALS AND METHODS:The anti-CD22-ScFv gene was designed using the variable heavy (VH) and light (VL) chain regions of the human RFB4 antibody and cloned into the pET28a vector, followed by expression in E. coli BL21 (DE3). The recombinant protein was purified by affinity chromatography and confirmed by SDS-PAGE. Anti-CD22-ScFv-β-CD Bio-MOFs were synthesized using glutaraldehyde and L-lysine as crosslinkers and subsequently loaded with DNR. The formation of the nanostructure was verified by ATR-FTIR spectroscopy and zeta potential analysis. Drug uptake and cytotoxic effects were evaluated in CD22-positive Raji cells and CD22-negative Jurkat cells using fluorescence microscopy, flow cytometry, and the MTT assay. RESULTS:Successful expression and purification of anti-CD22-ScFv were confirmed by SDS-PAGE. Characterization analyses verified the formation of anti-CD22-ScFv-β-CD-DNR Bio-MOFs. The targeted system facilitated efficient uptake of DNR in CD22-positive Raji cells and induced significant dose-dependent cytotoxicity. In contrast, minimal effects were observed in CD22-negative Jurkat cells. CONCLUSIONS:Anti-CD22-ScFv-β-CD-DNR Bio-MOFs demonstrate effective and selective delivery of DNR to CD22-expressing cells and may represent a promising targeted therapeutic approach for B-cell malignancies.
