Design of PEG-grafted-PLA nanoparticles as oral permeability enhancer for P-gp substrate drug model Famotidine

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.

Keywords:

• Caco-2
• Famotidine
• nanoparticles
• permeability
• P-gp
• PLA
• PEG

Acknowledgements

This work was supported in part by a grant of Fond Quebecois de la Recherche en Nature et Technologie (FQRNT) The authors wish to thank COREALIS Pharma Inc, Montreal for their help in doing some analysis. Mohamed Mokhtar thanks the Ministry of Higher Education, Libya for granting him a scholarship during his Ph.D.

Disclosure statement

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the article.

Additional information

Funding

This work was supported in part by a grant of Fond Quebecois de la Recherche en Nature et Technologie (FQRNT).