Department of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, Naresuan University, Phitsanulok, Thailand.
J Ocul Pharmacol Ther. 2013 Mar;29(2):200-7. doi: 10.1089/jop.2012.0193. Epub 2013 Jan 28.
PURPOSE: To characterize nanoparticles produced by self-assembly of oppositely charged polymers, cationic chitosan (CS), and anionic dextran sulfate (DS), for drug delivery to the ocular surface. The goal is to overcome the short residence time of topical drugs through their sustained release from mucoadhesive nanoparticles. METHODS: Chitosan-dextran sulfate nanoparticles (CDNs) were produced by mixing CS and DS; polyethylene glycol-400 was used as a surface stabilizing agent. Fourier transform infrared spectroscopy (FTIR) spectra of CS, DS, and CDNs were determined in the wavenumber range of 4,000-700 cm(-1) to assess the ionic interactions in the formation of CDNs. The physicochemical properties, entrapment efficacy, and dissolution profile of CDNs were investigated using Rhodamine B (RhB) and Nile Red (NR) as drug analogs. The mucoadhesiveness of the CDNs was assessed by imaging the retention of the fluorescein isothiocyanate-labeled CDNs on the cornea ex vivo, which was subjected to shear stress by a steady stream of saline solution. RESULTS: CDNs were obtained by the polyelectrolyte complexation technique. The FTIR spectra of CDNs showed spectral shifts in the amine and sulfate regions, confirming an involvement of electrostatic interactions between cationic CS and anionic DS. The CDNs were spherical in shape and segregated. They possessed a particle size of ~400 nm with a polydispersity index of 0.3 and exhibited a zeta potential of ~40 mV. A high entrapment efficacy of up to 80% was observed with both RhB and NR. In the dissolution experiments, NR was released from CDNs within 60 min, but RhB was not released. This indicates that the release of drugs could depend on their molecular interactions with the particle. Exposure of CDNs to lysozyme, which is found in tears, had no effect on the mean particle size or the surface charge. Instillation of NR, RhB, and FITC in the presence of saline irrigation resulted in their rapid disappearance (<5 min) from the corneal surface. In contrast, fluorescent CDNs showed retention on the cornea even after 60 min. CONCLUSIONS: Cationic and biocompatible mucoadhesive CDNs have been developed for sustained drug delivery to the ocular surface. The CDNs were stable to lysozyme and showed prolonged adherence to the corneal surface.
目的：通过自组装带相反电荷的聚合物（阳离子壳聚糖[CS]和阴离子葡聚糖硫酸酯[DS]）来表征纳米颗粒，以用于眼部表面的药物传递。目标是通过从粘膜粘附性纳米颗粒中持续释放来克服局部药物的短停留时间。
方法：通过混合 CS 和 DS 来生产壳聚糖-葡聚糖硫酸酯纳米颗粒（CDNs）；聚乙二醇-400 用作表面稳定剂。在 4,000-700 cm(-1) 的波数范围内确定 CS、DS 和 CDNs 的傅里叶变换红外（FTIR）光谱，以评估形成 CDNs 中的离子相互作用。使用罗丹明 B（RhB）和尼罗红（NR）作为药物类似物研究 CDNs 的物理化学性质、包封效率和溶解曲线。通过成像在角膜上保留异硫氰酸荧光素标记的 CDNs 来评估 CDNs 的粘膜粘附性，角膜在稳定的盐水溶液流的剪切力下。
结果：通过聚电解质络合技术获得 CDNs。CDNs 的 FTIR 光谱显示胺和硫酸盐区域的光谱位移，证实阳离子 CS 和阴离子 DS 之间存在静电相互作用。CDNs 呈球形且分离。它们的粒径约为 400nm，多分散指数为 0.3，并表现出约 40mV 的 ζ 电位。观察到 RhB 和 NR 的包封效率高达 80%。在溶解实验中，NR 在 60 分钟内从 CDNs 中释放，但 RhB 未释放。这表明药物的释放可能取决于它们与颗粒的分子相互作用。将 CDNs 暴露于泪液中发现的溶菌酶对平均粒径或表面电荷没有影响。在盐水冲洗的情况下滴注 NR、RhB 和 FITC 会导致它们在角膜表面迅速消失（<5 分钟）。相比之下，荧光 CDNs 甚至在 60 分钟后仍保留在角膜上。
结论：已经开发出阳离子和生物相容的粘膜粘附性 CDNs 用于眼部表面的持续药物输送。CDNs 对溶菌酶稳定，并显示出对角膜表面的延长粘附性。
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