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新型抗血管内皮生长因子药物雷珠单抗负载的聚乳酸-羟基乙酸共聚物/聚乳酸共聚物纳米胶束的制备,用于在年龄相关性黄斑变性治疗中进行长效眼内给药。

Novel fabrication of anti-VEGF drug ranibizumab loaded PLGA/PLA co-polymeric nanomicelles for long-acting intraocular delivery in the treatment of age-related macular degeneration therapy.

作者信息

Xu Jin-Feng, Wang Yan-Ping, Liu Xiao-Hua

机构信息

Department of Ophthalmology, Dongying People's Hospital, Dongying 257001, China.

出版信息

Regen Ther. 2024 Aug 27;26:620-634. doi: 10.1016/j.reth.2024.06.019. eCollection 2024 Jun.

DOI:10.1016/j.reth.2024.06.019
PMID:39281109
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11399609/
Abstract

Age associated macular degeneration is the 3rd primary cause of blind fundus diseases globally. A reliable and long-lasting method of intraocular drug delivery is still needed. Herein, this study was aim to develop the novel fabrication of ranibizumab loaded co-polymeric nanomicelles (Rabz-CP-NMs) for AMD. The CMC of co-polymeric nanomicelles was determined to be low, at 6.2 μg/ml. The ring copolymerization method was employed to fabricate the NMs and characterize via FTIR, XRD, TEM, DLS and Zeta potential. Rabz-CP-NMs was spherical shape with 10-50 nm in size. Stable and prolonged drug release was achieved with the Rabz from CP-NMs at 48 h. D407 and ARPE19 ocular cell lines showed dose-dependent cell viability with Rabz-CP-NMs. The Rabz-CP-NMs also had less toxicity, higher uptake, lower cell death and prolonged VEGF-A inhibition, as shown by cytoviability assay. Thus, Rabz-CP-NMs were safe for ocular use, suggesting that could be used to improve intraocular AMD treatment.

摘要

年龄相关性黄斑变性是全球眼底疾病致盲的第三大主要原因。目前仍需要一种可靠且持久的眼内给药方法。在此,本研究旨在开发用于治疗年龄相关性黄斑变性的新型载有雷珠单抗的共聚物纳米胶束(Rabz-CP-NMs)。共聚物纳米胶束的临界胶束浓度测定为低浓度,即6.2μg/ml。采用环化共聚法制备纳米胶束,并通过傅里叶变换红外光谱(FTIR)、X射线衍射(XRD)、透射电子显微镜(TEM)、动态光散射(DLS)和zeta电位进行表征。Rabz-CP-NMs呈球形,尺寸为10-50nm。在48小时内,CP-NMs中的雷珠单抗实现了稳定且持久的药物释放。D407和ARPE19眼细胞系对Rabz-CP-NMs表现出剂量依赖性细胞活力。细胞活力测定表明,Rabz-CP-NMs还具有较低的毒性、较高的摄取率、较低的细胞死亡率以及延长的血管内皮生长因子A(VEGF-A)抑制作用。因此,Rabz-CP-NMs用于眼部是安全的,这表明其可用于改善年龄相关性黄斑变性的眼内治疗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cfad/11399609/bb9cac364945/gr13.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cfad/11399609/bb9cac364945/gr13.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cfad/11399609/077cb8205d5e/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cfad/11399609/2ce562bdab20/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cfad/11399609/a54e9d81ea30/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cfad/11399609/18a82b30276a/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cfad/11399609/962ddfbcb5fc/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cfad/11399609/3ca1b404b23b/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cfad/11399609/b0e4b88523aa/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cfad/11399609/a3b258ac9bbe/gr8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cfad/11399609/daf6807258a0/gr9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cfad/11399609/664e00c8e8cd/gr10.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cfad/11399609/05b0ef58edd6/gr11.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cfad/11399609/9aed67ae7ce1/gr12.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cfad/11399609/bb9cac364945/gr13.jpg

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