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
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. Determin...
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Veröffentlicht in: | International journal of nanomedicine 2020-01, Vol.15, p.9373-9387 |
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Format: | Artikel |
Sprache: | eng |
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Zusammenfassung: | 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.
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.
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.
2-HP-β-CD/PLGA NPs are a promising nanoplatform for localized ocular drug delivery through topical administration. |
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ISSN: | 1178-2013 1176-9114 1178-2013 |
DOI: | 10.2147/IJN.S272750 |