Optimization of Linagliptin-loaded polymersomes via response surface methodology: A repurposed therapeutic strategy for hepatic encephalopathy prevention

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Date

2025-03-28

Journal Title

Journal ISSN

Volume Title

Type

Article

Publisher

Editions de Sante

Series Info

Journal of Drug Delivery Science and Technology ; Volume 108 , June 2025 , Article number 106855

Abstract

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.

Description

SJR 2024 0.817 Q1 H-Index 89

Keywords

Hepatic encephalopathy, Linagliptin, Polymersomes

Citation

Sweed, N. M., Elbalkiny, H. T., Magdy, E., Ramadan, M., Mahmoud, S., Mohamed, T., Mannaa, I. S., & Zaafan, M. A. (2025). Optimization of Linagliptin-Loaded polymersomes via response surface Methodology: A Repurposed therapeutic Strategy for Hepatic encephalopathy Prevention. Journal of Drug Delivery Science and Technology, 106855. https://doi.org/10.1016/j.jddst.2025.106855