Hanoi University of Pharmacy

Antimicrobial peptides (AMPs) represent a promising class of alternatives to conventional antibiotics. In this study, we compared the structural and functional properties of three synthetic undecapeptides: the anionic Cn-AMP2 and its N-terminally acetylated derivative (Ac-CnAMP2), versus the cationic α-helical peptide BP52. While BP52 exhibited strong antibacterial activity against both Gram-positive and Gram-negative bacteria, Cn-AMP2 and Ac-CnAMP2 showed no measurable antibacterial effects up to 128µM. Hemolysis assays revealed that BP52 caused mild to moderate lysis of red blood cells, whereas the anionic peptides were non-hemolytic. Molecular dynamics simulations confirmed the enhanced membrane insertion, clustering behavior, and bilayer disruption induced by BP52, in contrast to the limited interaction profiles of Cn-AMP2. These findings underscore the importance of positive charge, helical conformation, and amphipathic topology in driving membrane action and offer insights for designing optimized AMP-based therapeutics.

Objective: Gastroretentive systems are well-known to improve solubility and absorption of weakly basic drugs, but effective gastric mucoadhesion remains challenging. This study aimed to evaluate mucoadhesive properties of a novel polymer, partially neutralized polyacrylate (PNP), and its potential application in mucoadhesive tablets to enhance bioavailability and therapeutic performance of a model weakly base drug, l-tetrahydropalmatine (l-THP), which requires sustained release for anti-addiction effect. Methods: The mucoadhesive behavior of PNP was evaluated in comparison with two traditional adhesive polymers, chitosan and hydroxypropyl methylcellulose (HPMC) K4M using rheology, mucin-particle test and molecular docking. The mucoadhesive properties of tablets containing these polymers were further assessed by tensile testing and scanning electron microscopy. Then in vitro drug release test was performed, and in vivo bioavailability was conducted in dogs. Results: PNP exhibited significantly stronger interaction with mucin and PNP-based tablets showed better mucoadhesion than both reference polymers. These properties were attributed to strong hydrogen bonding and hydrophobic interactions with mucin, along with efficient diffusion and interpenetration of linear polymer chains into mucus layers. PNP-based tablets also effectively sustained drug release in vitro. In vivo study in dogs showed that PNP-based mucoadhesive tablets increased bioavailability of l-THP by 1.27-fold and prolonged the duration of plasma concentrations within therapeutic range compared with HPMC K4M tablets. The PNP formulation also enhanced bioavailability by 1.79-fold while reducing the maximum plasma concentration to 0.86-fold compared with immediate-release tablets. Conclusion: These findings highlight PNP as a promising mucoadhesive polymer for gastroretentive systems to improve bioavailability and therapeutic performance of weakly basic drugs.

The first objective of the study is to formulate and determine the stability of self-nanoemulsifying drug delivery systems containing progesterone in both in-vitro and in-vivo lipolysis simulated conditions. Another aim of the study was to compare the bioavailability of raw material, SNEDDS, and the reference product in the rabbit model. The high amount of cosolvent played an important role in maintaining the high nanoemulsion formation area, monodispersity, and drug loading capacity of SNEDDSs consisting of oleic acid, Tween 80, and ethanol. Under different in vitro severe conditions, including a hot-cold cycle, freeze-thaw cycle, and different pHs of gastrointestinal simulated mediums, there was no appearance of drug precipitation and phase separation of optimal SNEDDS. The cryo-TEM and dynamic light scattering study indicated that the size of the nanoemulsion was under 150 nm and monodispersity. The in vivo lipolysis simulated study then showed that the lower the amount of drug content loaded in SNEDDSs, the higher the proportion of Progesterone (PGT) existed in the colloidal phase, and the lower the risk of drug precipitation in the gastrointestinal medium. Especially, the percentage of PGT in the colloidal phase obtained from the digestion process of optimal SNEDDS was much higher than that from the reference product. Besides, the majority of drugs digested from Ultrogestan (R) existed in the precipitation phase. These in vitro results were consistent with a pharmacokinetics study in the rabbit model, which indicated that the oral bioavailability of SNEDDS was improved by around 2.95 and 5.40 times compared to the reference product and raw material, respectively.

Dexamethasone sodium phosphate (DSP), a hydrophilic corticosteroid, is widely used for inflammatory and autoimmune disorders; however, its topical efficacy is limited by poor skin permeation and short residence time, requiring frequent application. To overcome these limitations, PEG (polyethylene glycol)-modified niosomes (NSs) incorporated into polymeric hydrogel and patch matrices were developed as a transdermal platform for sustained drug delivery and improved transdermal permeation. DSP-loaded NSs were prepared by the ethanol injection method. The effects of formulation variables (cholesterol, surfactant, and excipients including poloxamer, PEG, and hydroxypropyl methylcellulose) were investigated. Vesicles were characterized for particle size (Z), polydispersity index (PDI), zeta potential, encapsulation efficiency (EE), morphology (SEM), and compatibility (FTIR). A design of experiments was applied to elucidate the roles of PEG and HPMC. Optimized NSs were incorporated into hydrogels (Carbopol, HPMC, NaCMC) and solid HPMC-based patches, then evaluated for drug release, ex vivo skin permeation, and stability. PEG-modified NSs increased significantly EE (26.68 ± 0.02

Aqueous bio-based hydrotropic solutions (ABHS) were investigated as green solvents for extracting glycyrrhizic acid (GA), a major amphiphilic triterpenoid saponin from licorice. Conventional and bio-based hydrotropes were screened under ultrasound-assisted extraction, with pentane-1,2-diol (PED) identified as the most effective solvent. Under optimized conditions (67.9% ABHS concentration, liquid-solid ratio of 49.9 mL g-1, extraction time of 17.0 min, and extraction temperature of 70 °C), ABHS achieved high GA extraction yield of 79.43 mg g-1, markedly outperforming conventional aqueous alcohols (≈49 mg g-1) and reported eutectic solvents (45.47-61.29 mg g-1). Extraction kinetics followed a second-order model, with a low apparent activation energy of 19.84 kJ mol-1, indicating a diffusion-controlled extraction process. Quantum chemical analyses, including electrostatic potential mapping, interaction region indicator analysis, and binding energy evaluation, revealed cooperative stabilization of both polar glycosidic units and weakly polar triterpenoid domains of GA in ABHS, with a calculated binding energy of -19.798 kcal mol-1, significantly stronger than those observed for water (-12.137 kcal mol-1) and ethanol (-15.307 kcal mol-1). An integrated macroporous resin-based strategy enabled efficient GA recovery with a recovery efficiency of 92.98% and high GA content (80.31%), while maintaining stable extraction performance and solvent recovery above 95.50% over three reuse cycles. Furthermore, GA-enriched fraction obtained using ABHS exhibited enhanced nitric oxide inhibitory activity without detectable cytotoxic effects on normal human cells, as supported by molecular docking analysis. In this context, the present study establishes ABHS as efficient, sustainable, and mechanistically transparent platforms for GA extraction, offering a promising green strategy for amphiphilic triterpenoid saponins.