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Ya-Chun Chu,1,2,* Hsu-Wei Fang,2,3,* Yu-Yi Wu,1 Yu-Jun Tang,1 Erh-Hsuan Hsieh,1 YiZhou She,4 Che-Yi Chang,1 I-Chan Lin,5,6 Yin-Ju Chen,1,7– 9 Guei-Sheung Liu,1,10– 12 Ching-Li Tseng1,8,9,13 1Graduate Institute of Biomedical Materials and Tissue Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei City, Taiwan; 2Department of Chemical Engineering and Biotechnology, National Taipei University of Technology, Taipei City, Taiwan; 3Institute of Biomedical Engineering and Nanomedicine, National Health Research Institutes, Miaoli County, Taiwan; 4School of Biomedical Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei City, Taiwan; 5Department of Ophthalmology, Wan Fang Hospital, Taipei Medical University, Taipei City, Taiwan; 6Department of Ophthalmology, School of Medicine, College of Medicine, Taipei Medical University, Taipei City, Taiwan; 7Department of Radiation Oncology, Taipei Medical University Hospital, Taipei City, Taiwan; 8International Ph.D. Program in Biomedical Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei City, Taiwan; 9Center for Precision Medicine and Translational Cancer Research, Taipei Medical University Hospital, Taipei City, Taiwan; 10Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, East Melbourne, VIC, Australia; 11Ophthalmology, Department of Surgery, University of Melbourne, East Melbourne, VIC, Australia; 12Menzies Institute for Medical Research, University of Tasmania, Hobart, TAS, Australia; 13Research Center of Biomedical Device, College of Biomedical Engineering, Taipei Medical University, Taipei City, Taiwan*These authors contributed equally to this workCorrespondence: Ching-Li Tseng, Tel +886 2 2736 1661 (ext. 5214), Email chingli@tmu.edu.twBackground: Corneal neovascularization (NV) is a process of abnormal vessel growth into the transparent cornea from the limbus and can disturb the light passing through the cornea, resulting in vision loss or even blindness. The use of nanomedicine as an effective therapeutic formulation in ophthalmology has led to higher drug bioavailability and a slow drug release rate. In this research, we designed and explored the feasibility of a new nanomedicine, gp91 ds-tat (gp91) peptide-encapsulated gelatin nanoparticles (GNP-gp91), for inhibiting corneal angiogenesis.Methods: GNP-gp91 were prepared by a two-step desolvation method. The characterization and cytocompatibility of GNP-gp91 were analyzed. The inhibition effect of GNP-gp91 on HUVEC cell migration and tube formation was observed by an inverted microscope. The drug retention test in mouse cornea was observed by in vivo imaging system, fluorescence microscope, and DAPI/TAMRA staining. Finally, the therapeutic efficacy and evaluation of neovascularization-related factors were conducted through the in vivo corneal NV mice model via topical delivery.Results: The prepared GNP-gp91 had a nano-scale diameter (550.6 nm) with positive charge (21.7 mV) slow-release behavior (25%, 240hr). In vitro test revealed that GNP-gp91 enhanced the inhibition of cell migration and tube formation capacity via higher internalization of HUVEC. Topical administration (eyedrops) of the GNP-gp91 significantly prolongs the retention time (46%, 20 min) in the mouse cornea. In chemically burned corneal neovascularization models, corneal vessel area with a significant reduction in GNP-gp91 group (7.89%) was revealed when compared with PBS (33.99%) and gp91 (19.67%) treated groups via every two days dosing. Moreover, GNP-gp91 significantly reduced the concentration of Nox2, VEGF and MMP9 in NV’s cornea.Conclusion: The nanomedicine, GNP-gp91, was successfully synthesized for ophthalmological application. These data suggest that GNP-gp91 contained eyedrops that not only have a longer retention time on the cornea but also can treat mice corneal NV effectively delivered in a low dosing frequency, GNP-gp91 eyedrops provides an alternative strategy for clinical ocular disease treatment in the culture.Graphical Abstract: Keywords: gp91 peptide, gelatin, nanoparticles, ocular retention, control release, corneal neovascularization, eye drops |
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