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用于盐酸罗匹尼罗经鼻脑递药的聚合物/表面活性剂/环糊精杂化粒子的制备:体外和在体评价。

Fabricating Polymer/Surfactant/Cyclodextrin Hybrid Particles for Possible Nose-to-Brain Delivery of Ropinirole Hydrochloride: In Vitro and Ex Vivo Evaluation.

机构信息

Department of Pharmacy, School of Health Sciences, National and Kapodistrian University of Athens, Panepistimiopolis, 15771 Zografou, Greece.

School of Pharmacy, Chemistry Interdisciplinary Project (CHIP), University of Camerino, Via Madonna delle Carceri, 62032 Camerino, Italy.

出版信息

Int J Mol Sci. 2024 Jan 18;25(2):1162. doi: 10.3390/ijms25021162.

Abstract

Ropinirole is a non-ergolinic dopamine agonist used to manage Parkinson's disease and it is characterized by poor oral bioavailability. This study aimed to design and develop advanced drug delivery systems composed of poloxamer 407, a non-ionic surfactant (Tween 80), and cyclodextrins (methyl-β-CD or hydroxy-propyl-β-CD) for possible brain targeting of ropinirole after nasal administration for the treatment of Parkinson's disease. The hybrid systems were formed by the thin-film hydration method, followed by an extensive physicochemical and morphological characterization. The in vitro cytotoxicity of the systems on HEK293 cell lines was also tested. In vitro release and ex vivo mucosal permeation of ropinirole were assessed using Franz cells at 34 °C and with phosphate buffer solution at pH 5.6 in the donor compartment, simulating the conditions of the nasal cavity. The results indicated that the diffusion-controlled drug release exhibited a progressive increase throughout the experiment, while a proof-of-concept experiment on ex vivo permeation through rabbit nasal mucosa revealed a better performance of the prepared hybrid systems in comparison to ropinirole solution. The encouraging results in drug release and mucosal permeation indicate that these hybrid systems can serve as attractive platforms for effective and targeted nose-to-brain delivery of ropinirole with a possible application in Parkinson's disease. Further ex vivo and in vivo studies to support the results of the present work are ongoing.

摘要

罗匹尼罗是一种非麦角灵类多巴胺激动剂,用于治疗帕金森病,其特点是口服生物利用度差。本研究旨在设计和开发由泊洛沙姆 407、非离子表面活性剂(吐温 80)和环糊精(甲基-β-CD 或羟丙基-β-CD)组成的先进药物传递系统,以便罗匹尼罗经鼻腔给药后可能用于治疗帕金森病的脑部靶向。混合系统通过薄膜水化法形成,然后进行广泛的物理化学和形态学表征。还测试了系统对 HEK293 细胞系的体外细胞毒性。使用 Franz 细胞在 34°C 下,在供体腔中使用 pH 5.6 的磷酸盐缓冲溶液,模拟鼻腔条件,评估罗匹尼罗的体外释放和离体黏膜渗透。结果表明,扩散控制的药物释放在整个实验过程中逐渐增加,而通过兔鼻黏膜进行的体外渗透的概念验证实验表明,与罗匹尼罗溶液相比,制备的混合系统具有更好的性能。药物释放和黏膜渗透的令人鼓舞的结果表明,这些混合系统可以作为有效和靶向的经鼻递药罗匹尼罗的有吸引力的平台,可能应用于帕金森病。正在进行支持本工作结果的进一步离体和体内研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/df52/10816138/271f09ef0a19/ijms-25-01162-g001.jpg

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