Poly(lactic-co-glycolic acid) based double emulsion nanoparticle as a carrier system to deliver glutathione sublingually
School of Pharmacy, Faculty of Medical and Health Science, University of Auckland, New Zealand
The sublingual delivery of drugs represents a continuing challenge, as well as an opportunity. In this study, a poly(lactic-co-glycolic acid) (PLGA) based Water-in-Oil-in-Water (w/o/w) double emulsion of nanoparticles was developed as potential platform technology, to generate sustained drug release profile and maximize the bioavailability of the glutathione (GSH). Two-level full factorial design was carried out based on different types and concentrations of the stabilizers used, and on varying sonication time. The optimal formulations were predicted with particle size of 232.57 ± 20.56 nm, zeta-potential of -12.33 ± 0.20 mV and entrapment efficiency of 77.04 ± 1.50%. Spherical particle morphology and uniform size was observed by scanning electron microscopy. Sustained release profile was achieved and the release kinetics was illustrated as a Korsmeyer-Peppas kinetic model. Moreover, in ex-vivo permeation studies over porcine mucosal epithelial membrane, approximately 2-fold increase in the transmucosal permeation of GSH was achieved when PVA and carbopol were incorporated with the drug delivery system, resulting in 21.9 ± 1.2% drug permeation and a permeation coefficient of (4.96 ± 0.36) × 10-6 cm∙sec-1. The developed PLGA nanoparticulate delivery system was able to elevate the retention time and resist saliva dissolution, providing a sustained drug release profile and relatively high transmucosal permeation of GSH.
Keywords: Sublingual delivery, PLGA Nanoparticles, Factorial design, Glutathione, Sustained release, Transmucosal permeation