Design of PEG-grafted-PLA nanoparticles as oral permeability enhancer for P-gp substrate drug model Famotidine. (2nd January 2017)

• Record Type: Journal Article
• Authors: Mokhtar, Mohamed; Gosselin, Patrick; Lacasse, François; Hildgen, Patrice
• Is Part Of: Journal of microencapsulation. Volume 34:Number 1(2017)
• Page Start: 91
• Page End: 103
• Publication Date: 2017-01-02
• Subjects: Caco-2 -- Famotidine -- nanoparticles -- permeability -- P-gp -- PLA -- PEG; Microencapsulation -- Periodicals; Controlled release technology -- Periodicals; 615.19
• DOI: 10.1080/02652048.2017.1290155
• Languages: English
• ISSNs: 0265-2048

Abstract

Abstract: Bioavailability of oral drugs can be limited by an intestinal excretion process mediated by P-glycoprotein (P-gp). Polyethylene glycol (PEG) is a known P-gp inhibitor. Dispersion of Famotidine (a P-gp substrate) within PEGylated nanoparticles (NPs) was used to improve its oral bioavailability. In this work, we evaluated the potential impact of NPs prepared from a grafted copolymer of polylactic acid and PEG on P-gp function by studying in vitro permeability of Famotidine across Caco-2 cells. Copolymers of PEG grafted on polylactic acid (PLA) backbone (PLA- g -PEG) were synthesised with 1 mol% and 5 mol% PEG vs. lactic acid monomer using PEG 750 and 2000 Da. The polymers were used to prepare Famotidine-loaded NPs and tested in vitro on Caco-2 cells. Significant decrease in basolateral-to-apical transport of Famotidine was observed when Famotidine was encapsulated in NPs prepared from PLA- g -PEG5%. NPs prepared from PLA- g -PEG5% are promising to improve oral bioavailability of P-gp substrates.