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纳米纤维涂层植入物:眼内应用于兔眼后的开发和安全性研究。

Nanofiber-coated implants: Development and safety after intravitreal application in rabbits.

机构信息

Federal University of Goias, Rua 240 w/n, CEP 74605-220, Goias, Goiania, Brazil; Pharmaceutical Research and Development, Ezequiel Dias Foundation, Rua Conde Pereira Carneiro 80, Gameleira, CEP 30510-010, Belo Horizonte, Minas Gerais, Brazil.

Pharmaceutical Research and Development, Ezequiel Dias Foundation, Rua Conde Pereira Carneiro 80, Gameleira, CEP 30510-010, Belo Horizonte, Minas Gerais, Brazil; Faculty of Pharmacy, Federal University of Minas Gerais, Av. Antônio Carlos 6627, Pampulha, CEP 31270-901, Belo Horizonte, Minas Gerais, Brazil.

出版信息

Int J Pharm. 2023 Apr 5;636:122809. doi: 10.1016/j.ijpharm.2023.122809. Epub 2023 Mar 7.

Abstract

Intravitreal injections are the preferred choice for drug administration to the posterior segment of the eye. However, the required frequent injections may cause complications to the patient and low adherence to the treatment. Intravitreal implants are able to maintain therapeutic levels for a long period. Biodegradable nanofibers can modulate drug release and allow the incorporation of fragile bioactive drugs. Age-related macular degeneration is one of the world major causes of blindness and irreversible vision loss. It involves the interaction between VEGF and inflammatory cells. In this work we developed nanofiber-coated intravitreal implants containing dexamethasone and bevacizumab for simultaneously delivery of these drugs. The implant was successfully prepared and the efficiency of the coating process was confirmed by scanning electron microscopy. Around 68% of dexamethasone was released in 35 days and 88% of bevacizumab in 48hs. The formulation presented activity in the reduction of vessels and was safe to the retina. It was not observed any clinical or histopathological change, neither alteration in retina function or thickness by electroretinogram and optical coherence tomography during 28 days. The nanofiber-coated implants of dexamethasone and bevacizumab may be considered as a new delivery system that can be effective for the treatment of AMD.

摘要

眼内注射是将药物递送至眼球后段的首选方法。然而,频繁的注射可能会给患者带来并发症,并且导致治疗依从性降低。眼内植入物能够长时间维持治疗水平。可生物降解的纳米纤维可以调节药物释放,并允许脆弱的生物活性药物的掺入。年龄相关性黄斑变性是世界上导致失明和不可逆转视力丧失的主要原因之一。它涉及 VEGF 和炎症细胞的相互作用。在这项工作中,我们开发了含有地塞米松和贝伐单抗的纳米纤维涂层眼内植入物,用于同时递送这些药物。成功制备了植入物,并通过扫描电子显微镜证实了涂层过程的效率。在 35 天内释放了约 68%的地塞米松,在 48 小时内释放了 88%的贝伐单抗。该制剂在减少血管方面具有活性,对视网膜是安全的。在 28 天内,通过视网膜电图和光学相干断层扫描未观察到任何临床或组织病理学变化,也未观察到视网膜功能或厚度的改变。地塞米松和贝伐单抗的纳米纤维涂层植入物可被视为一种新的给药系统,可有效治疗 AMD。

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