Multi-functional purine nucleoside-modified chitosan polymer micelles for improving the oral absorption of doxorubicin based on nucleoside transporter mediation.

Establishing experimental parameters for biphasic transfer in vitro lipolysis model.

Microparticle-based drug delivery systems have gained widespread recognition for their ability to enable sustained drug release. However, their utility in oral administration has been constrained by suboptimal gastrointestinal retention. This study systematically evaluated how engineered microparticle morphology and surface topography influence intestinal adhesion dynamics and drug release profiles. Through controlled modulation of surface roughness and particle geometry, we demonstrated that non-spherical architectures, particularly waterdrop-like microparticles (WDMPs), exhibited superior mucoadhesive properties, achieving 1.25-fold prolonged gastrointestinal retention time while maintaining optimal drug release kinetics (71.2% cumulative release over 10 h). In a murine inflammatory bowel disease (IBD) model, dexamethasone (DXM)-loaded WDMPs outperformed conventional free drug administration, manifesting in significantly improved therapeutic outcomes: 1.16-fold enhanced weight recovery, 1.27-fold greater colon length preservation, and superior histopathological scores. Notably, WDMPs also boosted oral bioavailability of micronutrients by 1.2-to-1.6-fold, highlighting its dual applicability for both pharmaceutical and nutraceutical delivery. These comprehensive findings positioned WDMPs as a transformative oral delivery platform that addresses longstanding challenges in gastrointestinal drug absorption, offering substantial potential for clinical translation. STATEMENT OF SIGNIFICANCE: This study demonstrates the potential of engineered microparticle morphology to address key challenges in oral drug delivery. By investigating the effects of particle morphology and surface topography on intestinal retention and drug release, we show that non-spherical, rough microparticles exhibit enhanced mucoadhesion and sustained drug release. Waterdrop-like Microparticles (WDMPs) provide a significant improvement in gastrointestinal retention and drug release kinetics. WDMPs also outperform free dexamethasone in a murine model of inflammatory bowel disease. Additionally, WDMPs enhance oral bioavailability for micronutrients, offering dual-purpose potential for pharmaceutical and nutraceutical applications. These findings highlight the critical role of microparticle morphology in optimizing drug delivery efficiency and underscore the versatility of WDMPs as a customizable platform for controlled release therapies.

Cistanoside A (Cis A) has received more attention because of its potential in the treatment of osteoporosis. However, its invivo process remains unknown. In this study, a simple liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the determination of cistanoside A in rat plasma, urine, and feces. After prepared by protein precipitation, cistanoside A and IS were separated on a Waters BEH C18 column with MS detection operated in positive multiple reaction monitoring mode. The method was fully validated and applied to the pharmacokinetic and excretion studies of cistanoside A in rats after intravenous (5 mg/kg) and oral (10, 20, and 40 mg/kg) administration. After intravenous administration, cistanoside A showed moderate clearance (0.52 ± 0.04 L*h/kg), low volume of distribution, and short terminal half-life (0.43 ± 0.03 h). After oral administration at doses of 10, 20, and 40 mg/kg, the system exposure increased lower than the increase of dose, and the oral bioavailabilities were 0.39%, 0.38%, and 0.23%, respectively. After oral administration, the average cumulative excretion rate was 0.03% in urine and 1.62% in feces at 24 h. In summary, this study defined the pharmacokinetic and excretion characteristics of cistanoside A in rats, which could provide useful information for its further development.

This study investigated whether coencapsulation of cannabidiol (CBD) and piperine (PIP) in food-grade nanostructured lipid carriers (NLCs) enhances the CBD oral bioavailability. NLCs containing long-chain fatty acids were formulated with 1% CBD and 1% PIP using either a CBD isolate (CBDiso) or a CBD extract (CBDext). Both systems showed high encapsulation efficiency and good stability over 28 days, with similar physicochemical properties. However, the CBD form strongly influenced digestion behavior: NLC-PIP-CBDiso exhibited high bioaccessibility for CBD (87 ± 5%), while NLC-PIP-CBDext showed markedly lower values (13 ± 4%). Based on these results, NLC-PIP-CBDiso was evaluated in a mouse pharmacokinetic study against NLC-CBDiso and CBD in hemp seed oil. While NLC-CBDiso did not improve absorption, NLC-PIP-CBDiso doubled the CBD systemic exposure, confirming that PIP codelivery significantly enhanced oral CBD absorption.

Discovery of a potent and orally available SOS1 inhibitor with antitumor efficacy in KRAS-mutant colorectal cancers.

Oral bioavailability of fenofibrate from melt-extruded phospholipid-containing solid dispersions: A rat study.

Rational design of a stable W/O lipid emulsion for enhanced oral delivery of vinblastine.

Invasive fungal infections (IFIs) are associated with high mortality rates and pose important therapeutic challenges because of the limited number of antifungal drug classes, their toxicity, and the emergence of resistance. Novel first-in-class antifungal agents have been recently approved (ibrexafungerp) or are currently being tested in clinical trials and are available via expanded access programs (olorofim, fosmanogepix). Among them, fosmanogepix (a prodrug of manogepix) represents a promising future therapeutic option for many IFIs because of its broad-spectrum antifungal activity and its favorable pharmacologic properties, such as oral bioavailability, extended tissue distribution (including the central nervous system), a good safety profile, and the absence of relevant drug-drug interactions. Fosmanogepix may become an interesting alternative option for the treatment of invasive candidiasis due to multidrug-resistant isolates (e.g., Candidozyma auris) or invasive aspergillosis due to azole-resistant Aspergillus spp. It also demonstrated very encouraging results for the treatment of invasive fusariosis and other refractory mold infections (e.g., scedosporiosis, lomentosporiosis). Novel gepix compounds have been developed and could make their niche in the future (e.g., APX2039, prodrug: APX2096, for cryptococcal meningitis, and APX2020, prodrug: APX2097, for coccidioidomycosis). This review discusses the future place of fosmanogepix in the antifungal armamentarium against IFIs.

Bergenin lipid prodrug nanoparticles: Synthesis, enhanced oral bioavailability, and mechanistic studies

Skin aging is a complex, multifactorial process driven by intrinsic biological factors and extrinsic environmental influences, with ultraviolet radiation playing a central role in accelerating structural and functional skin deterioration. A wide range of topical and systemic interventions have been proposed to prevent or reverse visible signs of skin aging. This review provides a critical evaluation of current skin aging interventions, including antioxidants, hormonal therapies, retinoids, hydrators such as hyaluronic acid, collagen peptides, and emerging senescence-targeting agents. Distinct from prior reviews, this work integrates both a pharmaceutical perspective, focusing on physicochemical properties, formulation stability, and dermal or oral bioavailability of active ingredients, and a methodological assessment of clinical evidence. While several skin aging interventions have been described to show benefits, their clinical effectiveness is often constrained by poor absorption, chemical instability, irritation, or limited mechanistic validation. The existing literature is characterized by small sample sizes, short study durations, subjective outcome measures, lack of appropriate controls, and frequent industry sponsorship, all of which limit the reliability and generalizability of reported outcomes. Retinoids remain the most consistently supported intervention, though tolerability issues persist, whereas evidence for antioxidants, hormonal therapies, hydrators and collagen peptides remains inconclusive. Overall, this review highlights a substantial gap between commercial claims and robust clinical evidence, underscoring the need for large-scale, well-controlled, independent trials with standardized, objective endpoints to establish safe, effective, and evidence-based strategies for healthy skin aging.

A highly specific and sensitive UPLC-MS/MS assay was established and validated for simultaneous determination of bullatine A and bullatolide B in rat plasma. Midazolam was employed as the internal standard (IS). Separation was performed on a Waters UPLC BEH C18 column using a gradient mobile phase consisting of methanol and 0.1% aqueous formic acid. Detection was carried out in the mode of multiple reaction monitoring (MRM), m/z 344.3 → 105.0 (bullatine A), m/z 438.6 → 154.2 (bullatine B), and m/z 326.2 → 291.4 (IS). Plasma proteins were effectively precipitated with acetonitrile prior to analysis. Good linear calibration curves (r2 > 0.995) were obtained in a range of 0.5-600 ng/mL for both analytes, with a limit of quantification of 0.5 ng/mL. Both intra- and inter-day precision (percent RSD) were less than 14% for bullatine A and less than 13% for bullatine B. Accuracy (percentage nominal concentration) was within the range of 91%-109% for all quality control levels. The proposed method exhibited excellent sensitivity and selectivity and was successfully applied to compare the pharmacokinetics following intravenous and oral administration in rats. The absolute oral bioavailability was determined to be 4.3% for bullatine A and 12.8% for bullatine B.

Pharmacokinetic-pharmacodynamic integration of shikimic acid in broilers: An indirect effect modeling approach.

Overcoming breast cancer resistance through targeted protein degradation and next generation chimeras.

Pongamol, a bioactive flavonoid derived from Pongamia pinnata (Fabaceae), has gained attention as a potential therapeutic agent for neurological disorders. Neurodegenerative and neuropsychiatric conditions such as Alzheimer's, Parkinson's, epilepsy, anxiety and depression are driven by oxidative stress, neuroinflammation, mitochondrial dysfunction, apoptosis and neurotransmitter imbalance, while current treatments remain largely symptomatic. This study evaluates the neuroprotective potential of pongamol using integrated in silico and experimental approaches. SwissADME analysis revealed favourable pharmacokinetic properties, including good oral bioavailability, high gastrointestinal absorption, blood-brain barrier permeability and non-substrate behaviour for P-glycoprotein. Prediction of activity spectra of substances predictions indicated antioxidant, anti-inflammatory, anti-Alzheimer's, antiparkinsonian, GABAergic, nootropic and cytoprotective activities. Target mapping identified interactions with potassium channels, melatonin receptors, phosphodiesterase-4D and kynurenine pathway enzymes. These findings were further supported by limited experimental studies suggesting possible attenuation of oxidative stress, suppression of neuroinflammation, inhibition of apoptosis and improvement in cognitive and behavioural outcomes in disease models, highlighting pongamol as a promising multitarget neuroprotective candidate.

Factors affecting perfluorooctanesulfonic acid (PFOS) serum concentration following fish consumption: implications for fish consumption advisories.

Improving Oral bioavailability: Lipid-polymeric nanoparticles of simvastatin and coenzyme Q10

Discovery of novel HDAC6 inhibitors based on the diphenyl-1,2,4-oxadiazole scaffold with potential efficacy in alleviating inflammation- and chemotherapy- associated mechanical hypersensitivity.

Design, synthesis and anti-bladder cancer activity of novel dihydroartemisinin-ibuprofen hybrids.

Visualized triglyceride-mimetic prodrugs: preparation, effect evaluation and mechanistic investigation of lymphatic transport.