Search Results (1,409)

Background/Objectives: Oleuropein is a bioactive phenolic compound from olive leaves with antimicrobial and antioxidant activity. This study aimed to develop a sprayable oral gel containing an oleuropein-rich aqueous extract and to evaluate its pharmaceutical performance antimicrobial efficacy and in ovo biological response. Methods: Oleuropein content was quantified using a validated chromatographic method. Polymeric systems were screened to select an optimized sprayable formulation. Physicochemical stability, dose uniformity, and antimicrobial activity against major cariogenic bacteria were evaluated. In ovo biological evaluation was conducted using the chick chorioallantoic membrane angiogenesis model together with histopathological examination of embryonic heart and liver tissues. Results: Oleuropein content was determined as 288.6 µg/mL in the olive leaf extract and 255.1 µg/mL in the final formulation. The optimized oral spray showed stable physicochemical properties, with pH maintained at 6.90 ± 0.02 and no relevant changes in viscosity during storage. The mean delivered dose per actuation was 0.128 ± 0.015 g, corresponding to 32.6 µg oleuropein per spray. The formulation exhibited inhibitory activity against all tested cariogenic microorganisms, with MIC values ranging from 13.3 to 170.7 µg/mL and MBC values generally two-fold higher. In the CAM assay, significant concentration- and time-dependent antiangiogenic effects were observed after 24–48 h at moderate and higher concentrations. Histopathological evaluation revealed dose-dependent acute degenerative and congestive changes in heart and liver tissues without evidence of fibrosis or steatosis. Conclusions: The oleuropein-based sprayable oral gel is a promising localized delivery system with adequate stability dose uniformity and antimicrobial efficacy. In ovo findings provide a conservative assessment of systemic exposure and support further development for oral biofilm and caries-related applications. Full article

Powder melt extrusion (PME) represents an alternative approach for personalized oral dosage forms. Furthermore, the utilization of agricultural waste has gained increasing attention because it helps reduce pollution from waste. This study investigated cellulose powders and short fibers from agricultural waste as supporting materials for the PME-based production of shape-changing levodopa printlets. Formulations containing cellulose powder (CP), cassava short fiber (CSF), and pineapple short fiber (PSF) demonstrated successful printing. The selected formulations were characterized for morphology, thermal transitions, crystallinity, shape-changing behavior, and drug release. CSF demonstrated superior printability, enhanced shape recovery, and the greatest reduction in crystallinity, supporting amorphous solid dispersion formation. Levodopa-loaded printlets showed uniform and high drug content. The formulation containing 5% CSF and levodopa exhibited the fastest initial release, attributed to its low crystallinity and Super Case II transport mechanism. Overall, this study highlights the feasibility of using natural cellulose as an additive in PME to develop sustainable, shape-changing drug delivery systems and advances PME knowledge by integrating agricultural waste derived cellulose fibers with levodopa processing that provide new insight into the material–process–performance relationship in PME systems. Full article

Background/Objectives: Canagliflozin (CFZ) is the first sodium glucose co-transporter 2 (SGLT-2) inhibitor and is characterized by poor water solubility and permeability, resulting in low oral bioavailability. In this study, a CFZ nanosuspension (CFZ-NS) was converted into a solid form to improve the physical stability of CFZ nanocrystals (CFZ-NCs) and to enable formulation as a tablet dosage form. Methods: To achieve adequate redispersibility of dried CFZ-NCs, fluid bed granulation and spray-drying methods were employed, and the effects of critical process parameters were investigated. The stability of spray-dried nanocrystal tablets (NCs-SD-TAB) was evaluated over a three-month period under storage conditions of 25 ± 2 °C with 60 ± 5% relative humidity (RH) and 40 ± 2 °C with 75 ± 5% RH. Results: The highest redispersibility index (94%) was obtained using the spray-drying method. Tablets prepared with spray-dried NCs-SD-TAB exhibited a significantly higher in vitro dissolution rate under non-sink conditions compared with control tablets prepared using unprocessed CFZ with the same excipients, as well as the marketed product. NCs-SD-TAB showed an approximately three-fold increase in drug release at 15 min in 0.1 N HCl, with a pH 4.5 acetate buffer and pH 6.8 phosphate buffer, which simulate gastrointestinal pH conditions, relative to the marketed product. Conclusions: Overall, these results indicate that nanocrystal technology represents a promising approach for CFZ as an improved oral drug-delivery system, primarily due to its solubility enhancement capabilities. Full article

FABP4 (fatty acid-binding protein 4) is a lipid chaperone and secreted adipokine linking dysregulated fatty acid handling with inflammation, cellular stress, and insulin resistance in obesity. By modulating nuclear receptor signaling (notably PPARγ) and enhancing NF-κB/MAPK activation in adipocytes and macrophages, FABP4 contributes to maladaptive adipose remodeling and systemic metabolic decline. This review critically summarizes recent preclinical evidence on natural bioactive compounds that regulate FABP4 expression and associated adipogenic programs in models of adipogenesis and diet-induced obesity. Data from 3T3-L1/OP9 adipocytes, rodent studies, and selected alternative models indicate that many plant-derived extracts and phytochemicals (e.g., polyphenols, saponins, coumarins, terpenoids, and fermented products) down-regulate FABP4 at mRNA and/or protein levels. These effects are frequently accompanied by suppression of PPARγ/C/EBPα/SREBP1c signaling, activation of AMPK-related pathways, reduced lipid accumulation, and improved metabolic outcomes including lower weight gain, reduced adipocyte hypertrophy, improved steatosis, and favorable serum lipid profiles. Natural compounds from non-plant sources (animal- and microbe-derived metabolites) further broaden FABP4-targeting strategies, supporting FABP4 as a cross-class therapeutic node. Key translational barriers include poor extract standardization, incomplete identification of active constituents, limited oral bioavailability, microbiome-dependent variability, and scarce clinical validation. Future work should prioritize well-characterized lead scaffolds, targeted delivery, rational combinations, and standardized, adequately powered clinical trials assessing dose, durability of FABP4 suppression, and cardiometabolic safety. Full article

Oral wound healing is a robust process; however, complications from surgery, systemic diseases, and aging can impair healing. While some treatments exist, regenerative therapies to promote mucosal wound healing remain limited. In recent years, there has been a significant rise in FDA-approved cell-based therapies; however, extracellular vesicles represent an emerging cell-free alternative that may mitigate risks associated with cellular therapies, including tumorigenesis and immunogenicity. These lipid-encapsulated nanovesicles can deliver therapeutic cargo, such as proteins, lipids, nucleic acids, or drugs, to the wound site. Extracellular vesicles can be derived from mesenchymal stromal cells, immune cells, bodily fluids, or bacteria, and engineered through genetic modification, preconditioning, or direct cargo loading to enhance therapeutic potency. Furthermore, advanced delivery platforms, including hydrogels, microneedles, and aerosols, allow for sustained and localized EV delivery to the oral wound site. This review examines differences between cutaneous and oral wound healing; factors that impair oral repair; extracellular vesicle sources and engineering strategies; and delivery strategies for developing EV-based therapeutics for oral wound healing. Full article

Background: Three-dimensional (3D) printing has been established in pharmaceutical sciences for preparing customized dosage forms with intricate release profiles. However, realizing this potential requires complex design strategies and the careful use of various excipients. This study was designed to evaluate the utility of hypromellose acetate succinate (HPMC-AS) as a singular release-modifying excipient for manufacturing oral solid dosage forms via fused deposition modeling (FDM) 3D printing. Methods: The scope of work encompassed comprehensive material characterization, formulation and production of drug-loaded filaments using hot-melt extrusion (HME), subsequent FDM 3D printing of tablet geometries, and in vitro dissolution studies using mebeverine hydrochloride (MebH) as the model drug. Results: Initial HME processing indicated that the HPMC-AS-based filaments were brittle, presenting technical challenges for direct 3D printing. This issue was successfully overcome by incorporating an additional preheating stage into the FDM printing process, which enabled production of the tablets. Dissolution analysis demonstrated that the 3D-printed mebeverine hydrochloride tablets exhibited delayed and sustained-release characteristics. Conclusions: These results confirm the viability of HPMC-AS as a standalone functional excipient in FDM 3D printing to produce tailored, complex drug delivery systems. Full article

Parenteral nutrition (PN) is essential for patients who are unable to tolerate oral or enteral feeding, providing them with necessary nutrients intravenously, including dextrose, amino acids, electrolytes, vitamins, trace elements, and lipid emulsions. Clinical pharmacists (CPs) play a critical role in PN management by ensuring proper formulation, monitoring therapy, preventing complications, and optimizing patient outcomes. In Saudi Arabia, limited literature exists on CPs’ involvement in total parenteral nutrition (TPN) administration, health information management (HIM) systems, and pharmacist staffing ratios. This paper examines the evolving role of CPs in PN management, addressing key challenges such as the optimal patient-to-CP ratio, the impact of HIM systems on PN prescribing, and the advantages and limitations of centralized versus decentralized PN prescription models. It highlights the need for standardized staffing levels, structured pharmacist training, and improved HIM integration to enhance workflow efficiency and prescribing accuracy. Additionally, the study examines how the adoption of advanced HIM systems can streamline documentation, reduce prescribing errors, and enhance interdisciplinary collaboration. This paper provides a framework for optimizing PN delivery, enhancing healthcare quality, and strengthening CPs’ contributions to nutrition support by addressing these factors. Implementing these recommendations will improve patient outcomes and establish a more efficient PN management system in Saudi Arabia, reinforcing the vital role of CPs in multidisciplinary care. Full article

Background/Objectives: This study developed a macitentan (MAC)–tadalafil (TAD) dry powder inhalation preparation using suspension-based spray drying to enhance pulmonary delivery and reduce systemic exposure to oral combination therapy in patients with pulmonary arterial hypertension (PAH). Methods: MAC–TAD composite powders were prepared by physically mixing or spray-drying aqueous ethanol suspensions at various MAC:TAD ratios. The lead M2-T8 was co-spray-dried with 5, 25, or 50% (w/w) L-leucine. Results: Spray-dried formulations exhibited narrower and more uniform particle size distributions (Dv50 2–6 µm; Dv90~10 µm) and higher emitted dose values than the physical mixtures. In the M2-T8 spray-dried formulation, TAD exhibited an elevated fine particle dose (FPD) (3073.45 ± 1312.30 μg), demonstrating improved aerosolization relative to the physical mixture, even outperforming the TAD-higher M1-T9 formulation (2896.83 ± 531.38 μg), suggesting that favorable interparticle adhesive interactions were developed during co-drying. The incorporation of 25% L-leucine produced the greatest improvement in dispersibility, increasing the FPD by ~31% for MAC and 17% for TAD, whereas excessive L-leucine (50%) reduced the aerosol performance. Powder X-ray diffraction and differential scanning calorimetry confirmed the retention of the MAC and TAD crystallinities, with L-leucine remaining either amorphous or partially crystalline. Conclusions: Suspension-based spray drying yielded MAC–TAD composite formulations with improved uniformity and aerosol performance. The optimized 2:8 formulation containing 25% L-leucine demonstrated the most efficient pulmonary deposition, supporting its potential as an inhaled combination therapy for the treatment of PAH. Full article

The past decade has witnessed an unprecedented transformation in breast cancer management, driven by parallel advances in targeted therapies, immunomodulation, drug-delivery technologies, and molecular diagnostic tools. This review summarizes the key achievements of 2015–2025, encompassing all major biological subtypes of breast cancer as well as technological innovations with substantial clinical relevance. In hormone receptor-positive (HR+)/HER2− disease, the integration of CDK4/6 inhibitors, modulators of the PI3K/AKT/mTOR pathway, oral Selective Estrogen Receptor Degraders (SERDs), and real-time monitoring of Estrogen Receptor 1 (ESR1) mutations has enabled clinicians to overcome endocrine resistance and dynamically tailor treatment based on evolving molecular alterations detected in circulating biomarkers. In HER2-positive breast cancer, treatment paradigms have been revolutionized by next-generation antibody–drug conjugates, advanced antibody formats, and technologies facilitating drug penetration across the blood–brain barrier, collectively improving systemic and central nervous system disease control. The most rapid progress has occurred in triple-negative breast cancer (TNBC), where synergistic strategies combining selective cytotoxicity via Antibody-Drug Conjugates (ADCs), DNA damage response inhibitors, immunotherapy, epigenetic modulation, and therapies targeting immunometabolic pathways have markedly expanded therapeutic opportunities for this historically challenging subtype. In parallel, photodynamic therapy has emerged as an investigational and predominantly local phototheranostic approach, incorporating nanocarriers, next-generation photosensitizers, and photoimmunotherapy capable of inducing immunogenic cell death and modulating antitumor immune responses. A defining feature of the past decade has been the surge in patent-driven innovation, encompassing multispecific antibodies, optimized ADC architectures, novel linker–payload designs, and advanced nanotechnological and photoactive delivery systems. By integrating data from clinical trials, molecular analyses, and patent landscapes, this review illustrates how multimechanistic, biomarker-guided therapies supported by advanced drug-delivery technologies are redefining contemporary precision oncology in breast cancer. The emerging therapeutic paradigm underscores the convergence of targeted therapy, immunomodulation, synthetic lethality, and localized immune-activating approaches, charting a path toward further personalization of treatment in the years ahead. Full article

Background: To overcome the gastrointestinal and hepatic toxicity of oral pirfenidone (PFD) in the treatment of idiopathic pulmonary fibrosis (IPF), this study systematically constructed a minimal-component, buffer-free pirfenidone aerosol inhalation solution (PFD-AIS), achieving lung-targeted delivery, reduced systemic exposure, and maintained antifibrotic efficacy. Methods: Analytical methods for PFD-AIS, covering content, related substances, aerodynamic particle size distribution (APSD), and delivered dose uniformity, were established. The prescription and preparation process of the formulation was optimized by evaluating its key quality attributes. Pharmacodynamic and pharmacokinetic evaluations of PFD-AIS were performed in a mouse lung-fibrosis model and SD rats. Results: The final specification of PFD-AIS was set to 40 mg:4 mL, containing 40 mg of PFD, 28 mg of sodium chloride, and 4 mL of injection water with a preparation process of 40 °C for 60 min and a pH range of 4–8. The PFD-AIS exhibited a fine particle fraction (FPF) of 56.1%, meeting the requirements for deep lung deposition. The delivered dose and delivery rate were 17.52 mg and 2.48 mg/min, respectively, both complying with inhalation formulation standards. In the bleomycin-induced IPF mouse model, the PFD-AIS markedly improved pulmonary fibrosis pathology, reduced the lung coefficient, and significantly lowered serum ALT/AST levels, indicating hepatic protection. In the SD rats, compared with oral dosing, PFD-AIS administration resulted in significantly lower AUC_0−t (−63%) and AUC_0–∞ (−67%) values, demonstrating a substantial reduction in systemic drug exposure. Conclusion: This work presents a complete, systematic chain—from formulation, process, and quality control to pharmacodynamics and pharmacokinetics—of a PFD-AIS. The PFD-AIS is effective and feasible, featuring a stable preparation process and controllable quality. Lung-directed drug delivery enhances PFD’s therapeutic efficacy, reduces systemic exposure and liver toxicity, and offers significant clinical advantages. Full article

Punicalagin, the major polyphenol in pomegranate peel, shows broad bioactivity but suffers from poor oral bioavailability. Whether hepatic or intestinal first-pass processes dominate this limitation remains unresolved. We developed a quantitative UPLC-MS/MS workflow to dissect punicalagin’s first-pass disposition and elimination in rats. Sprague–Dawley rats received punicalagin by intravenous, portal vein, oral, or intraduodenal dosing; plasma exposure was quantified by UPLC-MS/MS and analyzed noncompartmentally. We also profiled urinary and fecal excretion of punicalagin and key metabolites (punicalin, ellagic acid, urolithin C and urolithin A) to define biotransformation and clearance. Punicalagin displayed an absolute oral bioavailability of ~3.49%. First-pass analysis revealed modest hepatic extraction (~13.94%) but near-complete intestinal extraction (95.95%), identifying intestinal first-pass metabolism as the dominant barrier to systemic exposure. Consistently, parent and metabolites were eliminated mainly in feces, whereas urine contained only trace conjugated urolithin A. Collectively, these findings demonstrate that the poor oral bioavailability of punicalagin is driven primarily by extensive intestinal first-pass metabolism rather than hepatic clearance, and that its feces-dominant elimination is compatible with widespread hydrolysis and microbiota-mediated conversion within the gut. This work provides a pharmacokinetic framework to guide strategies aimed at improving oral delivery and systemic exposure of punicalagin. Full article

Background/Objective: Osimertinib (OSI) is a third-generation tyrosine kinase inhibitor approved for non-small cell lung cancer (NSCLC) therapy. OSI is administered orally; this route limits the amount of OSI reaching the tumor in the lungs and is associated with serious systemic toxicity. This study aimed to develop a dry powder inhalable formulation to provide tumor-targeted delivery and minimize systemic toxicity. To the best of our knowledge, this is the first study to prepare and evaluate a dry powder inhalation formulation of OSI. Methods: Chitosan-coated PLGA nanoparticles (PLGA-C NPs) encapsulating OSI were prepared using a single emulsion-solvent evaporation technique. PLGA-C NPs were assembled into respirable nanocomposite microparticles (NCMPs) via spray drying with L-leucine as a carrier. PLGA-C NPs were characterized for particle size, zeta-potential, encapsulation efficiency, and in vitro efficacy in A-549 cell line. NCMPs were evaluated for solid-state properties, aerosolization performance, stability and in vitro release. Results: PLGA-C NPs exhibited a particle size of 145.18 ± 3.0 nm, high encapsulation efficiency and a positive zeta potential. In vitro studies demonstrated a 3.6-fold reduction in IC50 compared to free OSI, superior antimigratory effects and enhanced cell cycle arrest. Solid-state characterization of NCMPs demonstrated drug encapsulation in the polymer without chemical interaction. NCMPs exhibited excellent aerosolization (mass median aerodynamic diameter of 1.09 ± 0.23 μm, fine particle fraction of 73.48 ± 8.6%) and sustained drug release (61.76 ± 3.9% at 24 h). Stability studies confirmed the physicochemical stability integrity. Conclusions: These findings suggest that this novel dry powder inhalable OSI formulation may improve therapeutic outcomes while reducing systemic toxicity. Full article

Nystatin is a polyene macrolide antibiotic with broad-spectrum antifungal activity and serves as a key therapeutic agent for superficial fungal infections. This review systematically elaborates on its multicomponent chemical nature, its mechanism of action targeting ergosterol, and highlights the potential adverse effects, such as cardiotoxicity, associated with impurities like RT6 (albonoursin). The fundamental analytical techniques for quality control are outlined. Furthermore, the clinical applications and combination therapy strategies of nystatin in treating oral diseases, vaginitis, and otitis externa are summarized in detail. Regarding biosynthesis, the assembly mechanism of nystatin A₁ via the type I polyketide synthase pathway and its subsequent modification processes are thoroughly discussed. Emphasis is placed on the latest advances and potential of gene-editing technologies, particularly CRISPR/Cas9, in the targeted knockout of genes responsible for toxic components and in optimizing production strains to enhance nystatin yield and purity. Finally, this review prospects the future development of nystatin towards improved safety and efficacy through structural optimization, innovative delivery systems, and synthetic biology strategies, aiming to provide a reference for its further research and clinical application. Full article

To improve the oral bioavailability of oleanolic acid (OA), this study developed a menthol–fatty acid-based hydrophobic deep eutectic solvent (HDES) system. Through a comprehensive evaluation using in vitro simulated digestion and Caco-2 cell transport models, the short-chain HDES was found to increase the apparent in vitro bioavailability index of OA by 9.3-fold compared to conventional ethanol systems, with efficacy showing clear fatty acid chain-length dependence. The mechanism was systematically investigated through spectral characterization and cellular studies, revealing a two-stage enhancement process: during the digestion phase, HDES significantly improved OA bioaccessibility to 14.30% compared to 4.90% with ethanol; during the absorption phase, it markedly increased cellular uptake to 25.79% versus 4.71% with ethanol. Molecular analysis indicated that the optimal hydrophobicity and diffusion properties of HDES contributed to this enhancement. This study reveals a fatty acid chain-length-dependent mechanism in HDES-facilitated OA delivery, providing a tunable strategy for enhancing the absorption of hydrophobic bioactive compounds. Full article

This review summarizes the role of nuclear factor erythroid 2–related factor 2 (Nrf2) as a common link between aging, neurodegeneration, and neuropathic pain. Aging is characterized by oxidative stress and constant inflammation, which coincides with reduced Nrf2 activity and weaker antioxidant responses, increasing vulnerability to diseases. In neurodegenerative disorders—including Alzheimer’s, Parkinson’s, Huntington’s disease, and amyotrophic lateral sclerosis—evidence indicates that impaired Nrf2 signaling contributes to oxidative damage, neuroinflammation, and mitochondrial dysfunction. Furthermore, in neuropathic pain, similar mechanisms are involved, and Nrf2 could play a role as a potential analgesic target because of its role in regulating cellular defense pathways. We also review natural Nrf2 modulators (e.g., flavonoids, other polyphenols, terpenoids, alkaloids), discussing their benefits alongside common translational limitations such as poor solubility, low oral bioavailability, rapid metabolism, and potential safety issues, including possible pro-oxidant effects and chemoresistance. We also outline future directions that should prioritize improving delivery systems, addressing NRF2/KEAP1 gene variations, evaluating combinations with standard therapies, exploring preventive applications, and defining dosing, treatment duration, and long-term safety. Overall, current evidence indicates that Nrf2 modulation is a practical, cross-cutting approach relevant to healthy aging and disease management. Full article