Zhang Zhaoliang, He Zhifen, Liang Renlong, Ma Yi, Huang Wenjuan, Jiang Rou, Shi Shuai, Chen Hao, Li Xingyi
Institute of Biomedical Engineering, School of Ophthalmology & Optometry and Eye Hospital, Wenzhou Medical University , 270 Xueyuan Road, Wenzhou 325027, P. R. China.
Biomacromolecules. 2016 Mar 14;17(3):798-807. doi: 10.1021/acs.biomac.5b01526. Epub 2016 Feb 12.
In this paper, we describe a simple method for constructing a micellar supramolecular hydrogel, composed of a low-molecular-weight methoxy poly(ethylene glycol) (Mn = 2000 Da) block polymer and α-cyclodextrin (α-CD), for topical ocular drug delivery. Adding aqueous block polymer micelles into an α-CD aqueous solution resulted in the formation of a micellar supramolecular hydrogel through host-guest inclusion. The effects of the drug payload, block polymer, and α-CD concentrations as well as the block polymer structure on gelation time were investigated. The resultant micellar supramolecular hydrogels were thoroughly characterized by X-ray diffraction, rheological studies, and scanning electron microscopy. The hydrogels exhibited thixotropic properties, which are beneficial to ocular drug delivery. In vitro release studies indicated that the α-CD concentration strongly influenced the release rate of diclofenac (DIC) from supramolecular hydrogel. The hydrogels showed relatively low cytotoxicity toward L-929 and HCEC cells and did not significantly affect the migration of the latter after 24 h incubation. The hydrogel was nonirritant toward the rabbit eye, as indicated by the Draize test, fluorescein staining, and histological observation. Nile Red-labeled micellar supramolecular hydrogel showed that it could significantly extend the retention time on the corneal surface in rabbits, compared with a plain micellar formulation. In vivo pharmacokinetics indicated that the hydrogel could greatly improve ocular drug bioavailability, compared with that of micellar formulation. Our results suggest that the micellar supramolecular hydrogel is a promising system for ocular drug delivery.
在本文中，我们描述了一种构建胶束超分子水凝胶的简单方法，该水凝胶由低分子量甲氧基聚（乙二醇）（Mn = 2000 Da）嵌段聚合物和α-环糊精（α-CD）组成，用于局部眼部给药。将水性嵌段聚合物胶束添加到α-CD水溶液中，通过主客体包合作用形成了胶束超分子水凝胶。研究了药物负载量、嵌段聚合物、α-CD浓度以及嵌段聚合物结构对凝胶化时间的影响。通过X射线衍射、流变学研究和扫描电子显微镜对所得胶束超分子水凝胶进行了全面表征。这些水凝胶表现出触变性，这对眼部给药有利。体外释放研究表明，α-CD浓度强烈影响双氯芬酸（DIC）从超分子水凝胶中的释放速率。该水凝胶对L-929和HCEC细胞显示出相对较低的细胞毒性，并且在孵育24小时后对后者的迁移没有显著影响。如Draize试验、荧光素染色和组织学观察所示，该水凝胶对兔眼无刺激性。尼罗红标记的胶束超分子水凝胶表明，与普通胶束制剂相比，它可以显著延长在兔角膜表面的保留时间。体内药代动力学表明，与胶束制剂相比，该水凝胶可以大大提高眼部药物的生物利用度。我们的结果表明，胶束超分子水凝胶是一种有前途的眼部给药系统。
