文献：

Ion-paired pirenzepine-loaded micelles as an ophthalmic delivery system for the treatment of myopia

文献链接：

https://www.sciencedirect.com/science/article/abs/pii/S1549963417300771

作者：

Yanan Li , Yong Zhang , Pengmei Li, Gujie Mi , Jiasheng Tua , Linlin Sund , Thomas J. Webster , Yan Shena

相关产品：

mPEG-PDLLA

原文摘要：Myopia is one of the most common ocular disorders for which standard treatments, such as refractive surgery, often involve invasive procedures. Pirenzepine (PRZ), a muscarinic receptor antagonist, has been recognized as a promising candidate for the treatment of myopia,

but possesses poor ocular bioavailability. The overall objective of this study was to prepare PRZ-sorbic acid complexes suitable to be encapsulated into micelles with high efficiency for optimal ophthalmic delivery. The results demonstrated that sorbic acid, used as the counter ion, had the most significant effects in increasing octanol–water distribution coefficient of PRZ as well as improving its corneal permeability in vitro among various counter ions tested. In vivo absorption results showed that a 1.5 times higher bioavailability was achieved by the addition of sorbic acid at 1:1 ratio. Cytotoxicity study in vitro and the biocompatibility study in vivo indicated that the micelles did not cause significant toxicities on the eyes.

mPEG-PDLLA自组装的胶束对tumor和健康哺乳动物细胞都显示出较小的细胞有害性，具有核壳结构，大小均匀。吡嗪平（PRZ）是一种Solifenacin。研究的总体目的是用mPEG-PDLLA制备适合的胶束复合物，方便后续应用。mPEG-PDLLA作为PRZ的载体，通过内吞作用和内吞体渗透促进内化过程，可将PRZ的可用性增加2倍，这通常与药物的自由悬液有关。制备过程如下：

PRZ/SA眼科胶束的制备

有机酸对PRZ负载mPEG-PDLLA胶束的制备 ——制备了PRZ/SA 负载mPEG-PDLLA胶束。简单地说，将HPMC（1%、2%、4%和6%）加入水（第一部分）中，混合至均匀分散。将 mPEG-PDLLA和有机酸PRZ溶解在磷酸盐缓冲液溶液（pH = 5.1）中，使用氢氧化钠溶液（第二部分）调整混合物的pH至5.1（第二部分）。第二部分与凝胶无菌混合。混合物高温高压压一段时间。将混合物冷却到室温后，得到的均质溶液。

图：PRZ/SA眼用胶束的形态学

结论：SA可以增强PRZ mPEG-PDLLA胶束的经角膜渗透，并增加PRZ在体内的生物利用度。通过适当的反离子对形成高度亲水的离子药物已被证明具有良好的应用前景。本研究证明了配合物在SA和PRZ之间形成了离子对，并可以成功地制成胶束，以提高PRZ的载药效率。研究结果还表明，在mPEG-PDLLA胶束中，SA和PRZ之间的络合降低了复合物的极性，并导致了PRZ在体内的生物利用度的明显改变。