RESUMO
This study aimed to develop a self-nanoemulsifying drug delivery system (SNE) for sinapic acid (SA) to improve its solubility and antiviral activity. Optimal components for the SA-SNE formulation were selected, including Labrafil as the oil, Cremophor EL as the surfactant, and Transcutol as the co-surfactant. The formulation was optimized using surface response design, and the optimized SA-SNE formulation exhibited a small globule size of 83.6 nm, high solubility up to 127.1 ± 3.3, and a 100% transmittance. In vitro release studies demonstrated rapid and high SA release from the formulation. Pharmacokinetic analysis showed improved bioavailability by 2.43 times, and the optimized SA-SNE formulation exhibited potent antiviral activity against SARS-CoV-2. The developed SA-SNE formulation can enhance SA's therapeutic efficacy by improving its solubility, bioavailability, and antiviral activity. Further in silico, modeling, and Gaussian accelerated molecular dynamics (GaMD)-based studies revealed that SA could interact with and inhibit the viral main protease (Mpro). This research contributes to developing effective drug delivery systems for poorly soluble drugs like SA, opening new possibilities for their application via nebulization in SARS-CoV-2 therapy.
RESUMO
The aim of this study was to develop and optimize a betahistine dihydrochloride (BH) thermoreversible bioadhesive gel intended for transdermal delivery. The gels were obtained via cold method. A full factorial design was employed to investigate the joint effect of Poloxamer 407 concentration (18 and 20%), adhesive polymer type (Polyvinyl pyrolidone, Hydroxypropyl methylcellulose, and Carbopol 934), and adhesive polymer concentration (0.5 and 1.5%) on gelling temperature, viscosity at 37 °C, and adhesion strength. Data collected were analyzed using multiple linear regression. A desirability index approach with relative importance weight was used to choose the most desirable formulation. F4 (20% Poloxamer+1.5% Carbopol) was selected for further characterization. F4 released 96.97% drug in 12 h across hairless rat skin. F4 gelation temperature and time were 36 ± 0.35 °C, and 6 ± 0.7 min, respectively. F4 adhesive force was 8835.68 dyne/cm2. F4 was tested for its appetite suppressing effect in a rat model and it was evaluated histopathologically. Rats' chow intake and weight gain was significantly decreased with no signs of inflammation or lipolysis when the optimized BH gel formulation, F4, was compared with untreated animals and animals treated with BH free gel. The results suggest that BH is percutaneously absorbed from the gel base and that the BH gel is tolerable. The desirability index approach with relative importance weight of responses was effective in determination of the optimum formulation. BH is systemically effective and well-tolerated when applied topically in hydrogel-based systems. The Carbopol-Poloxamer gel is a promising modality for transdermal delivery of BH.