Browsing by Author "Heba T. Elbalkiny"

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    Beyond erectile dysfunction: Optimization of vardenafil dihydrochloride for hepatic encephalopathy prophylaxis using hybrid lipid polymeric nanoparticles formulation
    (Editions de Sante, 2025-03-06) Marwa H.S. Dawoud; Heba T. Elbalkiny; Yasmeen E.M. Gharib; Sara A.A. Fakkar; Rowaa Saber; Marry E. Yanni; Mai A. Zaafan
    Vardenafil dihydrochloride (VD), a phosphodiesterase-5 (PDE5) is widely used to treat erectile dysfunction, but recent studies suggested its potential for other diseases such as hepatic encephalopathy. However, VD suffers poor solubility and oral bioavailability, and significant first-pass metabolism. This study aims to enhance the bioavailability of VD by employing two combined approaches: formulation of VD into hybrid lipid-polymeric nanoparticles (HLPNPs), and incorporating piperine, a known bioavailability enhancer, to investigate its potential in preventing hepatic encephalopathy. HLPNPs were developed using homogenization/ultrasonication technique, with a one-factor design testing chitosan, oleic acid, or sodium alginate as the helper polymers. Oleic acid showed the best results and was used to prepare the optimized formula (O1), which had a particle size of 128 ± 2.8 nm, a polydispersity index of 0.173 ± 0.07, an entrapment efficiency of 93 ± 1.8 %, and a zeta potential of − 32 ± 1.67 mV. O1 showed a sustained drug release profile, with approximately 70 % of VD released over 72 h. O2 was then prepared with the addition of piperine, resulting in a longer residence time of 717 min compared to O1 (94 min) in the pharmacokinetics study. O1 showed a twofold increase in the bioavailability compared to the unformulated VD while O2 exhibited a ninefold increase. The improvement was confirmed by the higher Cmax from 9 ng/mL for standard VD to 13 ng/mL and 22 ng/mL for O1 and O2, respectively. In hepatic encephalopathy-induced mice model, O2 showed promising efficacy, with significant improvements in liver enzymes, ammonia levels, hippocampal BDNF levels, cGMP levels, and hippocampal GluR1 and P-CREB levels. These findings suggest that combining VD into HLPNPs with piperine is an effective strategy to overcome its bioavailability limitations and enhance its therapeutic potential.
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    Optimization of Linagliptin-loaded polymersomes via response surface methodology: A repurposed therapeutic strategy for hepatic encephalopathy prevention
    (Editions de Sante, 2025-03-28) Nabila M. Sweed; Heba T. Elbalkiny; Eslam Magdy; Mahitab Ramadan; Shahin Mahmoud; Toka Mohamed; Islam S. Mannaa; Mai A. Zaafan
    This study aims to prepare linagliptin-loaded polymersomes in order to enhance its stability, bioavailability, and to investigate its potential in the prophylaxis against hepatic encephalopathy (HE). Polymersomes were formulated using solvent injection technique and optimized using D-optimal design, where the effect of drug to polymer ratio (X1) and polymer type, whether Poly (D, L-lactic-co-glycolide) or polycaprolactone (X2) were studied. Fifteen formulae were prepared and evaluated for entrapment efficiency % (Y1), particle size (Y2), and zeta potential (Y3). The optimized formula was prepared using polycaprolactone polymer with a drug to polymer ratio of 1:8.9. The optimized formula showed an entrapment efficiency % of 73 ± 1.04 %, a particle size of 184.1 ± 1.45 nm, and a zeta potential of − 21.2 ± 0.97 mV. In-vitro drug release showed remarkable sustained release profile for linagliptin-loaded polymersomes as compared to the standard linagliptin. In-vivo pharmacokinetic studies in rats showed a 262 % increase in bioavailability of linagliptin-loaded polymersomes. Moreover, linagliptin-loaded polymersomes showed promising results in a rat model of hepatic encephalopathy, with marked improvement in markers such as alanine transaminase (ALT), aspartate aminotransferase (AST), ammonia levels, and hippocampus brain-derived neurotrophic factor levels (BDNF). Our results showed that the optimized linagliptin-loaded polymersomes formula is a promising drug delivery system for enhancing linagliptin bioavailability, offering potential therapeutic benefits for managing HE and other diseases requiring sustained release and enhanced bioavailability.