Ge Jiang, Yuqin Wen, Huanhuan Jia, Qingchun Xie, Jiashu Lu, Junfeng Ban, Junming Chen, Yanzhong Chen, Fohua Chen, Haoting Li, Qingchun Ni, Yifeng Wen, Jindi Qiu, Zhufen Lu, Hao Wu, Zhenjie Mo, Yan Zhang, and Zhijiong Wang
Ge Jiang,1,* Huanhuan Jia,2,* Jindi Qiu,1,* Zhenjie Mo,1 Yifeng Wen,1 Yan Zhang,1 Yuqin Wen,1 Qingchun Xie,1,3– 5 Junfeng Ban,1,3– 5,* Zhufen Lu,1,3– 5 Yanzhong Chen,1,3– 5 Hao Wu,6 Qingchun Ni,7 Fohua Chen,1 Jiashu Lu,1 Zhijiong Wang,1 Haoting Li,1 Junming Chen1 1Guangdong Pharmaceutical University, Guangzhou, People‘s Republic of China; 2Key Laboratory of Guangdong Laboratory Animals, Guangdong Laboratory Animals Monitoring Institute, Guangzhou, People‘s Republic of China; 3Guangdong Provincial Key Laboratory of Advanced Drug Delivery Systems, Guangdong Pharmaceutical University, Guangzhou, People‘s Republic of China; 4Guangdong Provincial Engineering Center of Topical Precision Drug Delivery System, Center for Drug Research and Development, Guangdong Pharmaceutical University, Guangzhou, People‘s Republic of China; 5R&D Innovation Team for Controlled-Release Microparticle Drug Delivery System, Guangdong Pharmaceutical University, Guangzhou, People‘s Republic of China; 6Community Health Service Center of South China Agricultural University, Guangzhou, People‘s Republic of China; 7Guangzhou General Pharmaceutical Research Institute Co., Ltd, Guangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhufen Lu; Yanzhong ChenGuangdong Provincial Key Laboratory of Advanced Drug Delivery Systems, Guangdong Pharmaceutical University, Guangzhou 510006, People‘s Republic of ChinaTel +86 20 39352506Email luzhufen@163.com doctor.c@163.comPurpose: 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: ocular drug delivery, PLGA nanoparticle, ocular barrier, oligosaccharide, local bioavailability, triamcinolone acetonide, eye drop administration