Barbault-Foucher S, Gref R, Russo P, Guechot J, Bochot A
UMR, CNRS 8612, Faculté de Pharmacie, Université de Paris-Sud, 5 Rue Jean-Baptiste Clément, 92296 Châtenay Malabry Cedex, France.
J Control Release. 2002 Oct 30;83(3):365-75. doi: 10.1016/s0168-3659(02)00207-9.
This study was performed to design a new ocular drug delivery system based on poly-epsilon-caprolactone (PCL) biodegradable nanospheres (NS) coated with a bioadhesive polymer, hyaluronic acid (HA), in order to combine ophthalmic prolonged action with the ease of application. The aim of this work was to investigate three strategies to attach HA on NS surface: (1) coating the core by chain entanglement with HA; (2) coating NS by HA adsorption; (3) coating NS by electrostatic interactions between negatively charged HA and a cationic surfactant (stearylamine, SA, or benzalkonium chloride, BKC). A radioimmunoassay technique, usually used for HA quantification in serum, was transposed to determine the amount of HA on the NS. The results show that HA is strongly attached on NS positively charged by cationic surfactant. This system is stable and not influenced by dilution. These results show the possibility of using cationic surfactants to obtain a HA coating by electrostatic interactions. BKC, approved for ophthalmic administration, was retained because it was more firmly anchored within the PCL matrix and the amount of HA attached was high (41.6 microg HA/mg PCL). Moreover, the yield of fixation reached 50%. Therefore, by using a simple preparation method, it was possible to obtain stable HA and intact HA-coated NS.
本研究旨在设计一种新型眼部给药系统，该系统基于聚己内酯（PCL）可生物降解纳米球（NS），并包覆有生物粘附聚合物透明质酸（HA），以便将眼部长效作用与易于应用相结合。这项工作的目的是研究三种将HA附着在NS表面的策略：（1）通过与HA的链缠结包覆核心；（2）通过HA吸附包覆NS；（3）通过带负电荷的HA与阳离子表面活性剂（硬脂胺，SA，或苯扎氯铵，BKC）之间的静电相互作用包覆NS。一种通常用于血清中HA定量的放射免疫分析技术被用于测定NS上HA的量。结果表明，HA强烈附着在由阳离子表面活性剂带正电的NS上。该系统稳定且不受稀释影响。这些结果表明利用阳离子表面活性剂通过静电相互作用获得HA涂层的可能性。由于BKC已获批准用于眼部给药，且其更牢固地锚定在PCL基质中且附着的HA量高（41.6μg HA/mg PCL），因此被选用。此外，固定产率达到50%。因此，通过使用简单的制备方法，有可能获得稳定的HA和完整的HA包覆NS。
