Ge Jiang1, Huanhuan Jia2, Jindi Qiu1, Junfeng Ban1,3,4,5, Zhenjie Mo1, Yifeng Wen1, Yan Zhang1, Yuqin Wen1, Qingchun Xie1,3,4,5, Zhufen Lu1,3,4,5, Yanzhong Chen1,3,4,5, Hao Wu6, Qingchun Ni7, Fohua Chen1, Jiashu Lu1, Zhijiong Wang1, Haoting Li1, Junming Chen1. 1. Guangdong Pharmaceutical University, Guangzhou, People's Republic of China. 2. Key Laboratory of Guangdong Laboratory Animals, Guangdong Laboratory Animals Monitoring Institute, Guangzhou, People's Republic of China. 3. Guangdong Provincial Key Laboratory of Advanced Drug Delivery Systems, Guangdong Pharmaceutical University, Guangzhou, People's Republic of China. 4. Guangdong Provincial Engineering Center of Topical Precision Drug Delivery System, Center for Drug Research and Development, Guangdong Pharmaceutical University, Guangzhou, People's Republic of China. 5. R&D Innovation Team for Controlled-Release Microparticle Drug Delivery System, Guangdong Pharmaceutical University, Guangzhou, People's Republic of China. 6. Community Health Service Center of South China Agricultural University, Guangzhou, People's Republic of China. 7. Guangzhou General Pharmaceutical Research Institute Co., Ltd, Guangzhou, People's Republic of China.
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.
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.
Authors: May Abou-ElNour; Rania A H Ishak; Mattia Tiboni; Giulia Bonacucina; Marco Cespi; Luca Casettari; Mahmoud E Soliman; Ahmed S Geneidi Journal: J Control Release Date: 2019-07-22 Impact factor: 9.776