Chitosan nanoparticles:: a new vehicle for the improvement of the delivery of drugs to the ocular surface.: Application to cyclosporin A
Chitosan nanoparticles:: a new vehicle for the improvement of the delivery of drugs to the ocular surface.: Application to cyclosporin A
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DOI：
10.1016/s0378-5173(01)00760-8
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发表时间：
2001-08-14
影响因子：
5.8
通讯作者：
Alonso, MJ
中科院分区：
文献类型：
--
作者：
De Campos, AM;Sánchez, A;Alonso, MJ
目前眼外疾病管理的局限性包括不能在不损害眼内结构和/或全身药物暴露的情况下提供长期眼外药物递送。在本研究中，壳聚糖（CS）纳米粒作为一种新的载体，用于改善药物输送到眼粘膜的潜力进行了研究。选择环孢菌素A（CyA）作为模型化合物，因为它对治疗这些局部疾病的潜在有用性。离子凝胶化技术方便地修改，以产生CyA负载CS纳米粒子。这些纳米颗粒的平均尺寸为293 nm，zeta电位为+37 mV，CyA缔合效率和负载量高（分别为73%和9%）。在水槽条件下进行的体外释放研究显示，在第一个小时内快速释放，随后在24小时内逐渐释放药物。体内实验表明，在向兔局部滴注负载CyA的CS纳米颗粒后，有可能在眼外组织中达到治疗浓度（即，角膜和结膜）同时维持内眼结构中可忽略或不可检测的CyA水平（即，虹膜/睫状体和房水）、血液和血浆。这些水平显著高于滴注含有CyA的CS溶液和CyA水悬浮液后获得的水平。从这些结果中，我们可以得出结论，CS纳米颗粒可能代表一个有趣的车辆，以提高临床上具有挑战性的药物的治疗指数，在眼外水平的潜在应用。(C)2001 Elsevier Science B. V.保留所有权利。
Present limitations in the management of extraocular diseases include the inability to provide long-term extraocular drug delivery without compromising intraocular structures and/or systemic drug exposure. In the present study, the potential of chitosan (CS) nanoparticles as a new vehicle for the improvement of the delivery of drugs to the ocular mucosa was investigated. Cyclosporin A (CyA) was chosen as a model compound because of its potential usefulness for the treatment of these local diseases. An ionic gelation technique was conveniently modified in order to produce CyA-loaded CS nanoparticles. These nanoparticles had a mean size of 293 nm, a zeta potential of + 37 mV and high CyA association efficiency and loading (73 and 9%, respectively). In vitro release studies, performed under sink conditions, revealed a fast release during the first hour followed by a more gradual drug release during a 24-h period. In vivo experiments showed that, following topical instillation of CyA-loaded CS nanoparticles to rabbits, it was possible to achieve therapeutic concentrations in external ocular tissues (i.e., cornea and conjunctiva) during at least 48 h while maintaining negligible or undetectable CyA levels in inner ocular structures (i.e., iris/ciliary body and aqueous humour), blood and plasma. These levels were significantly higher than those obtained following instillation of a CS solution containing CyA and an aqueous CyA suspension. From these results, we can conclude that CS nanoparticles may represent an interesting vehicle in order to enhance the therapeutic index of clinically challenging drugs with potential application at extraocular level. (C) 2001 Elsevier Science B.V. All rights reserved.