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
Scientific Journal Rankings
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