PLGA Nanoparticle Platform for Trans-Ocular Barrier to Enhance Drug Delivery: A Comparative Study Based on the Application of Oligosaccharides in the Outer Membrane of Carriers

Int J Nanomedicine. 2020 Nov 24:15:9373-9387. doi: 10.2147/IJN.S272750. eCollection 2020.

Abstract

Purpose: The trans-ocular barrier is a key factor limiting the therapeutic efficacy of triamcinolone acetonide. We developed a poly(lactic-co-glycolic acid) nanoparticles (PLGA NPs) surface modified respectively with 2-hydroxypropyl-β-cyclodextrin (2-HP-β-CD), chitosan oligosaccharide and trehalose. Determination of the drug/nanoparticles interactions, characterization of the nanoparticles, in vivo ocular compatibility tests, comparisons of their corneal permeability and their pharmacokinetics in aqueous humor were carried out.

Methods: All PLGA NPs were prepared by the single emulsion and evaporation method and the drug-nanoparticle interaction was studied. The physiochemical features and in vitro corneal permeability of NPs were characterized while the aqueous humor pharmacokinetics was performed to evaluate in vivo corneal permeability of NPs. Ocular compatibility of NPs was investigated through Draize and histopathological test.

Results: The PLGA NPs with lactide/glycolide ratio of 50:50 and small particle size (molecular weight 10 kDa) achieved optimal drug release and corneal permeability. Surface modification with different oligosaccharides resulted in uniform particle sizes and similar drug-nanoparticle interactions, although 2-HP-β-CD/PLGA NPs showed the highest entrapment efficiency. In vitro evaluation and aqueous humor pharmacokinetics further revealed that 2-HP-β-CD/PLGA NPs had greater trans-ocular permeation and retention compared to chitosan oligosaccharide/PLGA and trehalose/PLGA NPs. No ocular irritation in vivo was detected after applying modified/unmodified PLGA NPs to rabbit's eyes.

Conclusion: 2-HP-β-CD/PLGA NPs are a promising nanoplatform for localized ocular drug delivery through topical administration.

Keywords: PLGA nanoparticle; eye drop administration; local bioavailability; ocular barrier; ocular drug delivery; oligosaccharide; triamcinolone acetonide.

Publication types

  • Comparative Study

MeSH terms

  • 2-Hydroxypropyl-beta-cyclodextrin / chemistry*
  • Animals
  • Cornea / metabolism*
  • Drug Carriers / chemistry*
  • Drug Liberation
  • Membranes, Artificial*
  • Nanoparticles / chemistry*
  • Oligosaccharides / chemistry*
  • Particle Size
  • Permeability
  • Polylactic Acid-Polyglycolic Acid Copolymer / chemistry*
  • Rabbits

Substances

  • Drug Carriers
  • Membranes, Artificial
  • Oligosaccharides
  • 2-Hydroxypropyl-beta-cyclodextrin
  • Polylactic Acid-Polyglycolic Acid Copolymer

Grants and funding

This work was supported by the Guangdong “Climbing” Program for Undergraduates (2021); The Natural Science Foundation of Guangdong Province (Grant Number 2019A1515011018); The planned Science and Technology Project of Guangdong Province (2017B020231001); Guangdong Graduate Education Innovation Program: Project Funded by Guangdong Province Joint Training Graduate Demonstration Base (Guangzhou General Pharmaceutical Research Institute Co., Ltd.) Guangdong Pharmaceutical University “Innovation and Enhancing Project”; National Natural Science Foundation of China (81941010); National Innovation and Entrepreneurship Training Program for College Students (Grant Number 201910573004).