Search Results (1,016)

Objectives: Herpetrione (HPE) is a bioactive lignan recognized for its hepatoprotective properties; however, it exhibits limited oral bioavailability. This study aimed to classify HPE within the framework of the biopharmaceutics classification system (BCS) and to develop a nanoparticle formulation. Methods: To this end, a comprehensive investigation was conducted, encompassing computer prediction analysis, equilibrium solubility measurements across the gastrointestinal pH range, Caco-2 bidirectional transportation, in situ single-pass intestinal perfusion (SPIP), and molecular docking with P-glycoprotein (P-gp). Results: In silico analyses suggested that HPE possesses low solubility and low permeability characteristics. Experimental assays revealed pH-dependent solubility and inherently low aqueous dissolution. Unlike the computer prediction results, Caco-2 studies revealed moderate permeability but a high efflux ratio, suggestive of possible P-gp substrate activity for HPE, a finding further supported by molecular docking simulations. Conversely, SPIP studies demonstrated that the effective permeability (P_eff) of jejunal intestinal segments exceeded the high-permeability threshold, thereby classifying HPE as a high-permeability drug. Based on these findings, HPE was classified as a BCS class II compound. To overcome its solubility-limited absorption, a nanoparticle was developed, resulting in a marked enhancement of both solubility and dissolution rates. Conclusions: These findings underscore the importance of integrating experimental biopharmaceutical evaluations with computational tools when designing delivery systems for natural products. Full article

Trimethylamine-N-oxide (TMAO), a gut microbiota-derived metabolite, is a known risk factor for cardiovascular disease. We previously showed that TMAO induces NLRP3 inflammasome activation and contributes to endothelial dysfunction. However, the upstream mechanisms linking TMAO to inflammasome activation and barrier injury remain unclear. In the present study, we examined whether membrane raft (MR) redox signaling contributes to TMAO-induced NLRP3 inflammasome activation and endothelial dysfunction. MR clustering, colocalization of MRs with NADPH oxidase subunits, inflammasome formation, and junction protein expression were assessed by Western blot analysis. RT-qPCR was performed to further assess the mRNA expression of junctional genes. Superoxide production was measured by electron spin resonance (ESR), caspase-1 activity was determined using a biochemical assay kit, IL-1β production was measured by ELISA, and endothelial permeability was evaluated using an FITC-dextran assay. TMAO increased MR clustering in endothelial cells in a dose-dependent manner. TMAO also enhanced the colocalization of MRs with p47phox and gp91phox, indicating the formation of an MR-associated redox signaling axis. In addition, TMAO increased superoxide production; promoted NLRP3 inflammasome formation; elevated caspase-1 activity and IL-1β production; reduced the expression of ZO-2, ZO-1, VE cadherin and occludin; and increased endothelial permeability. Pretreatment with the MR disruptor MCD, the NADPH oxidase inhibitor DPI, or the caspase-1 inhibitor WEHD significantly attenuated these TMAO-induced effects. These findings demonstrate that TMAO-mediated endothelial injury is dependent on the MR-associated redox signaling axis. TMAO promotes MR-associated redox signaling, leading to NADPH oxidase activation, superoxide generation, NLRP3 inflammasome activation, disruption of endothelial junction proteins, and barrier dysfunction. Targeting MR-associated signaling pathways may offer a novel therapeutic strategy to mitigate TMAO-induced vascular inflammation and endothelial dysfunction. Full article

Background: Nigella sativa L. is a medicinal plant widely recognized for its diverse pharmacological properties. This study aimed to evaluate the antioxidant, diuretic, and cytotoxic effects of an aqueous seed extract and its effects on selected biochemical parameters in rats. The pharmacokinetic potential of identified bioactive compounds was also investigated in silico. Methods: The aqueous extract was prepared by maceration. Antioxidant activity was assessed using DPPH, reducing power, and total antioxidant capacity (TAC) assays. We evaluated the diuretic effect in vivo in Wistar rats by measuring urinary concentrations of Na⁺, K⁺, Cl⁻, and creatinine, using furosemide as a reference drug. Cytotoxicity was assessed in splenocytes and thymocytes. We analyzed seven identified compounds in silico for physicochemical properties, Lipinski compliance, intestinal absorption, cytochrome P₄₅₀ inhibition, and blood–brain barrier permeability. Results: The extract showed significant antioxidant activity, with a DPPH IC₅₀ of 0.254 ± 0.002 mg/mL and a TAC of 125.01 ± 4.220 mg AAE/g. It significantly increased urinary electrolyte and urinary concentration, indicating a diuretic effect lower than that of furosemide. Plasma analyses showed decreased electrolyte concentrations and increased creatinine levels. Cell viability exceeded 90%, indicating no significant cytotoxicity. Most compounds complied with Lipinski’s rule of five and showed favorable predicted intestinal absorption, with limited cytochrome P₄₅₀ inhibition. Several compounds were predicted to cross the blood–brain barrier. Conclusions: The aqueous extract of N. sativa demonstrated antioxidant and diuretic activities without significant cytotoxicity. These findings support its pharmacological potential and warrant further investigation of its mechanisms of action and therapeutic relevance. Full article

Background/Objectives: Repurposing existing drugs may represent a promising strategy for effective cancer therapy. This study was the first to investigate the augmented antitumor therapeutic effect achieved by co-incorporating the NSAID Niflumic acid (NIF) with ceramides into PEGylated cerosomes (NIF-loaded PEG-CERs) in a novel platform that targets specifically the MAPK-ERK signaling pathway and miR-21-5p modulation. Methods: The prepared formulae were statistically optimized utilizing a full factorial design and the optimal formula (C5) was further incorporated into a topical gel and evaluated for ex vivo rat skin permeation, and tested in vivo in a subcutaneous solid Ehrlich carcinoma (SEC) mice model. Results: The optimal formula (C5) showed tubular elongated morphology with higher EE% (96.71 ± 0.0), lower vesicular size (VS) and PDI values, 292.95 ± 0.78 nm and 0.47 ± 0.0 respectively. A high ZP value (−37.5 ± 0.57 mV) was in accordance with stability results showing good stability of the optimal formula (C5). Permeability studies exhibited 2.02-fold higher skin permeation compared to pure NIF gel. A significant decrease in tumor volume and marked improvement in survival rate in SEC mice were confirmed by downregulation of EGFR, ERK1, ERK2, and miR-21-5p expression. Furthermore, an increase in total antioxidant capacity and caspase-3 levels was observed, accompanied by significant suppression in cyclin D1, MMP-2, COX-2, and MDA levels. Finally, histopathological analysis revealed the superior antitumor effect of C5 gel together with immunohistochemical assay showing the lowest BCL-2-positive staining, indicating the restoration of physiological apoptotic balance. Conclusions: Based on the previous findings, NIF-loaded PEG-CERs offer augmented therapeutic potential for efficient topical skin cancer management in an SEC mice model. Full article

This study investigated the neuroprotective potential of Xanthoceras sorbifolium Bunge (XSB) seed oil through fatty acid profiling, antioxidant assays, and in silico targeting of FABP7. Among the solvent-to-solid ratios tested, 1:20 (w/v) gave the highest oil yield (72.91%) and the strongest ABTS, DPPH, and FRAP activities. GC-MS identified 17 fatty acids from the 1:20 (w/v) oil extract, with linoleic acid (38.93%) and oleic acid (31.3%) as the major constituents. Following GC-MS fatty acid profiling, lipid structural characterization was performed using ¹H NMR and FT-IR. ADME/T prediction and BOILED-EGG analysis suggested favorable pharmacokinetic properties and BBB permeability for the selected fatty acids. Molecular docking and simulation revealed strong and stable interactions of five compounds with FABP7: nervonic acid (−6.1 kcal/mol), erucic acid (−6.002 kcal/mol), eicosadienoic acid (−6.08 kcal/mol), oleic acid (−6.03 kcal/mol), and linoleic acid (−6.00 kcal/mol), outperforming the native ligand, oleic acid (−5.8 kcal/mol). These findings indicate that XSB seed oil contains bioactive lipids with promising FABP7-targeted neuroprotective potential and warrant further investigation as therapeutic leads for neurodegenerative diseases. Full article

Staphylococcus aureus secretes multiple proteases that contribute to tissue damage and modulation of host immune responses. The glutamate-specific serine endopeptidase (VSPase) is secreted by S. aureus strain C-66; however, its effects on inflammatory signaling and vascular permeability remain poorly understood. In this study, we investigated the pro-inflammatory and vascular permeability-enhancing activities of VSPase and compared them with those of its catalytically inactive S237L mutant. In RAW 264.7 macrophages, VSPase induced the mRNA expression of TNF-α, IL-1β, IL-12β, MIP-2, cyclooxygenase-2, and prostaglandin E synthase. VSPase also increased TNF-α secretion in a concentration-dependent manner, whereas S237L elicited little or no comparable response. VSPase caused a rapid and transient reduction in cytosolic IκBα levels and increased NF-κB DNA-binding activity in nuclear extracts. Competition and supershift assays confirmed the specificity of the DNA–protein complex and demonstrated the presence of the p65 subunit. In a guinea pig Evans blue extravasation assay, intradermal administration of VSPase increased vascular leakage in a dose-related manner, whereas S237L produced minimal effects. Collectively, these findings demonstrate that VSPase induces pro-inflammatory mediator expression in association with activation of a p65-containing NF-κB complex and enhances vascular permeability in vivo. The markedly reduced activity of S237L further suggests that the catalytic activity of VSPase is closely associated with its inflammatory and vascular effects. VSPase may therefore contribute to host inflammatory responses and vascular dysfunction during staphylococcal infection. Full article

Acetaminophen (APAP) represents a major cause of drug-induced liver injury (DILI), and effective pharmacological interventions remain limited. Annexin A5 (AnxA5), a Ca²⁺-dependent phospholipid-binding protein, participates in diverse biological processes related to tissue repair. In this study, we evaluated AnxA5 expression in APAP-challenged mouse livers and clinical samples from patients with liver injury. Using hepatic cell lines AML12 and HepG2, we performed overexpression-based functional assays to assess the cytoprotective effects of AnxA5 against APAP toxicity. Co-immunoprecipitation assays were applied to characterize protein interactions, and mitochondrial functional parameters were measured to dissect the underlying molecular mechanism. We found that AnxA5 was significantly upregulated in both APAP exposed mice and APAP DILI patients. Cellular functional assays showed that AnxA5 overexpression mitigated APAP triggered cytotoxicity in AML12 and HepG2 cells. Mechanistically, AnxA5 bound to voltage dependent anion channel 1 (VDAC1), restrained VDAC1 mediated mitochondrial Ca²⁺ influx, and suppressed VDAC1 oligomerization, which further inhibited mitochondrial permeability transition pore (mPTP) opening. In an APAP-induced liver injury mouse model, exogenous recombinant AnxA5 treatment maintained mitochondrial integrity and ameliorated hepatic inflammation and liver damage. Collectively, our data reveal AnxA5 as an endogenous mitochondrial protective factor and support its therapeutic potential against APAP-induced liver injury. Full article

Ready-to-cook Asian moon scallop (RAM) may harbor seafood-associated spoilage and opportunistic pathogenic bacteria, leading to quality deterioration and food safety concerns. This study investigated the microbiological diversity, virulence-associated phenotypes, and antibacterial activity of chitooligosaccharide–epigallocatechin gallate conjugate (CEGC) combined with nisin against seafood-associated bacteria isolated from RAM. A total of 102 bacterial isolates were subjected to identification by MALDI-TOF/MS, with Vibrio, Aeromonas, and Shewanella as the predominant genera. Several isolates exhibited proteolytic and hemolytic activities, indicating spoilage potential and virulence-associated traits. Multivariate analysis showed that bacterial isolates differed widely in their antimicrobial susceptibility and virulence-associated phenotypes. Checkerboard assays demonstrated synergistic effects between CEGC and nisin against Vibrio parahaemolyticus and Vibrio fluvialis (FICI = 0.50). The additive effects were observed for the remaining strains, except an indifferent effect (FICI = 1.06) was found for A. hydrophila. The combined treatment markedly inhibited bacterial growth and biofilm formation, achieving approximately 95% biofilm reduction in V. parahaemolyticus. Confocal laser scanning microscopy and scanning electron microscopy revealed severe membrane disruption, increased permeability, cellular deformation, and collapse of biofilm architecture. Furthermore, CEGC–nisin effectively suppressed V. parahaemolyticus growth in cold-stored RAM. These findings demonstrate that CEGC combined with nisin is a promising natural antimicrobial strategy for improving seafood safety and reducing microbial spoilage in ready-to-cook seafood products. Full article

The neurovascular unit (NVU) is composed of a diverse array of cells and an extracellular matrix (ECM). Neural cells and blood vessels are intricately interconnected, forming a cohesive whole. Specific cellular components and structures within the NVU play an indispensable role in maintaining homeostasis of the central nervous system (CNS). With the advancement and maturation of cell co-culture technology, various three-dimensional (3D) NVU models continue to emerge, offering a more objective and comprehensive perspective for in vitro studies of CNS diseases. Specifically, these 3D NVU models include Transwell Chamber models, gel-polydimethylsiloxane (PDMS)-based 3D models, self-assembled NVU models and microfluidic NVU models, which reconstruct the complex NVU architecture to varying degrees. This review systematically summarizes multiple 3D construction strategies for in vitro NVU to overcome the limitations of conventional cellular tests or animal experiments, highlights the critical roles of biomimetic gel in recapitulating native cell-gel crosstalk, comparatively analyzes four major 3D NVU technical routes in terms of cellular composition, vascular morphology, barrier performance, and reproducibility, categorizes application scenarios of 3D NVU platforms oriented to practical research demands, including oxygen-glucose deprivation/reoxygenation (OGD/R) injury modeling, blood-brain barrier (BBB) permeability assay, CNS drug penetration screening, neuroinflammation and neurotoxicity evaluation, proposes practical principles for model selection under different experimental purposes, and concludes with current bottlenecks, including imperfect vascular network maturation and lack of unified evaluation criteria, together with future perspectives for standardized 3D NVU in vitro. By comparing the advantages and limitations of these approaches, we aim to clarify their optimal applicability for investigating specific pathological mechanisms and screening potential therapeutics. Full article

Background: Diabetic retinopathy (DR) is a leading cause of vision loss, with oxidative stress and inflammation serving as critical drivers of its onset and progression. Curcumin, a natural polyphenol, is known for its potent anti-inflammatory and antioxidant properties. Glial fibrillary acidic protein (GFAP) is commonly used as an indicator of retinal macroglial reactivity, whereas the NLRP3 inflammasome is an important mediator of inflammatory signaling in DR. We evaluated retinal vascular abnormalities and retinal GFAP immunoreactivity and examined whether these findings were accompanied by changes in retinal NLRP3 and IL-1β protein abundance and in the levels of cleaved caspase-1 and cleaved GSDMD. Methods: Diabetes was induced in 7-week-old rats via a single intraperitoneal injection of streptozotocin. Following the confirmation of hyperglycemia, curcumin was administered orally. To evaluate the effects, we performed trypsin digestion, haematoxylin and eosin (H&E) staining, fluorescein isothiocyanate (FITC)–dextran permeability assays, immunofluorescence staining, and Western blotting on the harvested retinas. Results: The DM group showed increased acellular capillary formation, vascular leakage, retinal GFAP immunoreactivity, NLRP3 and IL-1β protein abundance, and levels of cleaved caspase-1 and cleaved GSDMD. Compared with the untreated DM group, the DM + curcumin group showed lower values for all of these outcomes. Conclusions: In diabetic rats, oral administration of a curcumin-containing formulation was associated with fewer retinal vascular abnormalities and lower GFAP immunoreactivity, accompanied by parallel differences in inflammasome-related proteins. These findings support the potential of this formulation as an adjunctive therapeutic approach for early diabetic retinopathy. Full article

Micro- and nanoplastics (MNPs) are increasingly detected in human tissues, yet their polymer-specific effects on endothelial cells remain poorly understood, particularly at the placental and fetal level. We compared cadmium selenide quantum dot-labelled polypropylene (PP) and polyvinyl chloride (PVC) model nanoplastics (NPs) in human umbilical vein endothelial cells (HUVECs) using particle characterization, MTT assays, flow cytometry, confocal microscopy, apoptosis analysis, and synchrotron nano-X-ray fluorescence imaging. PP nanoplastics caused an early reduction in metabolic activity, showed the strongest cell-associated fluorescence, and produced the greatest increase in membrane permeability and late apoptotic/necrotic populations. PVC nanoplastics displayed a more punctate distribution with greater overlap with membrane-associated regions and induced a stronger increase in LC3B-positive vesicular structures. Nano-XRF detected Cd-enriched signals associated with the labelled particles and a polymer-specific Cd–Cl spatial association in PVC-exposed cells. Sulfur mapping further revealed localized sulfur-poor regions along the cell periphery in exposed cells, suggesting localized remodeling of peripheral membranes. These findings indicate that PP and PVC NPs interact differently with endothelial cells and elicit distinct structural and functional responses. Polymer composition should therefore be considered when assessing the vascular and prenatal effects of MNP exposure. Full article

Although the Pacific oyster (Crassostrea gigas) is a premium marine protein source, its neuroprotective peptidome remains largely uncharacterized. This study established an integrated in silico and in vitro pipeline to discover acetylcholinesterase (AChE)-targeting peptides with cellular AChE-regulating and neuroprotective peptides from simulated gastrointestinal digests of oyster. Peptidomic profiling identified 18,292 sequences, which were filtered down to seven candidates predicted to have favorable blood–brain barrier (BBB) permeability and to be non-toxic and non-allergenic (VPYPR, VPVHF, HHTF, PVHF, GPKPW, HWF, and KYW) via multi-step virtual screening. In cellular assays, simulated H₂O₂ injury (500 μM) reduced PC12 cell viability to 47.53 ± 4.53%. Compared with the model group, pretreatment with the three most potent candidates—HHTF, VPYPR, and VPVHF (200 μM)—significantly rescued injured cells, restoring cell viability to 88.31 ± 7.83%, 85.12 ± 3.35%, and 82.00 ± 3.47%, respectively (p < 0.05). These peptides effectively fortified cellular antioxidant defenses by increasing glutathione (GSH) levels to 24.24, 30.11, and 26.83 nmol/mg protein (from 20.22 nmol/mg protein in the model group) and superoxide dismutase (SOD) activity to 151.41, 153.97, and 151.96 U/mg protein (from 119.33 U/mg protein), while suppressing malondialdehyde (MDA) accumulation to 0.088, 0.064, and 0.086 nmol/mg protein (from 0.193 nmol/mg protein). Crucially, the peptides alleviated cholinergic dysfunction by normalizing the H₂O₂-induced elevation of intracellular AChE activity (11.39 nmol/min/mg protein) down to 7.02, 6.22, and 7.14 nmol/min/mg protein, respectively. Specifically, VPYPR (200 μM) restored AChE activity to a level (6.22 nmol/min/mg protein) that was not significantly different from that in the normal control group (p > 0.05). Molecular dynamics (MD) simulations (100 ns) and molecular mechanics Poisson–Boltzmann surface area (MM-PBSA) calculations identified VPYPR as the leading candidate with a remarkably low binding free energy of −49.74 ± 3.58 kcal/mol. This study demonstrates that oyster gastrointestinal digests are valuable reservoirs of multi-target neuroprotective ingredients and provides an efficient strategy for marine bioactive peptide discovery. Full article

Background/Objectives: Blood–brain barrier (BBB) permeability is a major practical obstacle in central nervous system (CNS) drug discovery, because only a small fraction of drug-like molecules achieve sufficient brain exposure. Methods: We present DeepBBB, a graph-based, data-composition-aware screening workflow for predicting BBB permeability and for constructing BBB-focused screening libraries from commercial chemical space. Rather than introducing a new graph-learning architecture, the workflow combines standard graph convolutional and graph-transformer models with deliberate control of training-set composition, commercial-library filtering, chemical-space profiling, and prospective experimental evaluation. Three model variants were trained on the Blood–Brain Barrier Database (B3DB): a baseline classifier/regressor pair (DeepBBB_V1_BC/RG), a variant trained with a more strongly negative-enriched configuration (DeepBBB_V2_BC), and a graph-transformer counterpart (DeepBBB_trans_BC/RG). Because the sample-level split assignments and per-compound predictions from the original runs were not recoverable, the archived summary metrics are reported descriptively in the main text and are not used to support calibration, scaffold-level validity, or generalization. Applying the workflow to the ChemDiv collection (~1.5 million compounds) and the Enamine REAL lead-like space (~1.7 billion compounds) produced three progressively more stringently filtered BBB-focused libraries (21,991; 4,808,885; and 151,790 compounds). Results: Analysis of available processed data indicated that the predicted BBB-permeable set occupies a compact, BBB-compatible property region. Physicochemical, fragment, and scaffold summaries were interpreted descriptively at the constructed-library level. In a first prospective campaign, one of 12 tested candidate compounds was PAMPA-BBB-positive (all-tested molecular-level positive fraction 8.3%; exact 95% CI 0.2–38.5%). In a second campaign, five of 35 tested candidate compounds were PAMPA-BBB-positive (14.3%; exact 95% CI 4.8–30.3%); 13 compounds were not quantifiable and were not treated as ordinary CNS-negative measurements, and the two campaigns differed in compound source, selection strategy, and assay setting, so the numerical difference is reported descriptively rather than causally. Conclusions: Together, these results support the feasibility of BBB-focused computational filtering and a PAMPA-BBB evaluation workflow for CNS-oriented discovery. Full article

Background: Antimicrobial resistance (AMR) is among the most pressing challenges in modern infectious medicine, driving progressive failure of standard antibacterial therapy and rising mortality from infections caused by multidrug-resistant (MDR) pathogens. Antibiotic potentiation through adjuvant compounds capable of restoring the activity of existing drugs represents a promising strategy to overcome resistance without developing fundamentally new antibacterial molecules. This study aimed to evaluate the antibiotic-potentiating activity of a dextrin/polyvinyl alcohol/iodine complex (D/PVA/I-1), developed at the Scientific Center for Anti-Infectious Drugs JSC (Almaty, Kazakhstan), against clinically relevant MDR reference strains. Methods: Nine reference strains, Staphylococcus aureus (ATCC 33591, BAA-39), Escherichia coli (ATCC BAA-196, BAA-2523), Klebsiella pneumoniae (ATCC BAA-2524, 700603), Acinetobacter baumannii (ATCC BAA-1790), Streptococcus pneumoniae (ATCC BAA-660), and Haemophilus influenzae (ATCC 33930), and two clinical isolates, P. aeruginosa SCAID PHRX1-2019 and E. coli SCAID WND1-2021, were tested. Antibiotic-potentiating activity was assessed by checkerboard assay with calculation of the fractional inhibitory concentration index (FICI); bactericidal kinetics were evaluated by time-kill analysis. The effect of D/PVA/I-1 on cytoplasmic membrane permeability was investigated using a crystal violet uptake assay. Results: Of 45 D/PVA/I-1–antibiotic combinations tested across nine antibiotics, synergy (FICI ≤ 0.5) was demonstrated in 44.4% of cases, partial synergy in 48.9%, and additive effects in 6.7%; no antagonistic interactions were detected. The most pronounced potentiating effect occurred against Gram-positive pathogens, particularly MRSA strains (66.7% synergistic combinations). Time-kill analysis confirmed suppression of the regrowth phenotype characteristic of MDR strains under monotherapy and restoration of bactericidal activity against antibiotics to which strains exhibited intrinsic resistance. D/PVA/I-1 induced a dose- and time-dependent increase in membrane permeability in both Gram-positive and Gram-negative organisms. Conclusions: D/PVA/I-1 is an effective broad-spectrum antibiotic potentiator and represents a promising basis for combination therapy regimens against MDR infections. Full article

Background/Objectives: The buccal mucosa offers a promising non-invasive route for systemic drug delivery, particularly for hydrophilic compounds like captopril (CAP), which exhibit low permeability and are subject to gastrointestinal instability and first-pass metabolism. This study aimed to develop and characterize captopril-loaded, chitosan-based mucoadhesive buccal films with different permeation enhancers and to evaluate their physicochemical properties, drug release, cytocompatibility, and in vitro transport across a TR146 buccal epithelial cell model. Methods: Films were prepared by the solvent-casting method using chitosan as the film-forming polymer. Different enhancers were investigated, including organic acid salts of chitosan (ascorbate, citrate, and lactate) and chemical permeation enhancers (sodium lauryl sulfate, polyethylene glycol 400, Span 20, and EDTA). Results: The resulting films exhibited acceptable thickness, moisture content, appropriate mechanical properties, and good mucoadhesive strength. In vitro dissolution studies demonstrated rapid CAP release, with >50% released within 15 min and near-complete release by 180 min across all formulations. Cytotoxicity assessment via a Neutral Red uptake assay in TR146 cells confirmed high cell viability (>81%) after 4 h of exposure, indicating good biocompatibility. In vitro permeation experiments revealed that films prepared with chitosan ascorbate and chitosan lactate enhanced CAP transport compared to other formulations, achieving the highest flux and apparent permeability coefficients. Conclusions: These findings demonstrate that chitosan ascorbate and lactate salts effectively improve the buccal permeability of captopril while maintaining good film properties and biocompatibility. This work highlights the potential of chitosan ascorbate- and lactate-based mucoadhesive films as an efficient platform for the buccal delivery of CAP. Full article