A hybrid genipin-crosslinked dual-sensitive hydrogel/nanostructured lipid carrier ocular drug delivery platform
A hybrid genipin-crosslinked dual-sensitive hydrogel/nanostructured lipid carrier ocular drug delivery platform
复制标题
混合京尼平交联双敏感水凝胶/纳米结构脂质载体眼部药物递送平台
DOI：
10.1016/j.ajps.2018.08.002
复制
发表时间：
2019
影响因子：
10.2
通讯作者：
Li Sanming
中科院分区：
文献类型：
--
作者：
Yu Yibin;Feng Ruoxi;Li Jinyu;Wang Yuanyuan;Song Yiming;Tan Guoxin;Liu D;an;Liu Wei;Yang Xinggang;Pan Hao;Li Sanming
本研究的目的是开发一种新的混合京尼平交联双敏感水凝胶/纳米结构脂质载体（NLC）药物传递平台。选择眼用抗炎药黄芩苷（BN）作为模型药物。采用熔融乳化结合超声技术制备了BN单键NLC。此外，通过与无毒交联剂京尼平（GP）的交联反应，制备了由羧甲基壳聚糖（CMCS）和泊洛沙姆407（F127）组成的pH和温度双重敏感性水凝胶。采用FTIR、NMR、XRD、SEM等手段对GP-CMCS/F127水凝胶进行了表征。溶胀研究表明GP-CMCS/F127水凝胶具有pH和温度敏感性。体外释放实验结果表明BN单键NLC凝胶剂能延长黄芩苷的释放时间，并与BN滴眼液和BN单键NLC进行了比较。BN单键NLC凝胶的表观渗透系数（Papp）是BN滴眼液的4.46倍。通过角膜水化水平的测定，证实BN单键NLC凝胶对角膜无明显刺激性。结果表明，NLC基水凝胶可延长角膜前停留时间。总之，基于杂化NLC的水凝胶具有应用于眼部药物递送的有希望的潜力。
The objective of this study was to develop a novel hybrid genipin-crosslinked dual-sensitive hydrogel/nanostructured lipid carrier (NLC) drug delivery platform. An ophthalmic anti-inflammatory drug, baicalin (BN) was chosen as the model drug. BNsingle bondNLC was prepared using melt-emulsification combined with ultra-sonication technique. Additionally, a dual pH- and thermo-sensitive hydrogel composed of carboxymethyl chitosan (CMCS) and poloxamer 407 (F127) was fabricated by a cross-linking reaction with a nontoxic crosslinker genipin (GP). GP-CMCS/F127 hydrogel was characterized by FTIR, NMR, XRD and SEM. The swelling studies showed GP-CMCS/F127 hydrogel was both pH- and thermo-sensitive. The results ofin vitrorelease suggested BNsingle bondNLC gel can prolong the release of baicalin comparing with BN eye drops and BNsingle bondNLC.Ex vivocornea permeation study was evaluated using Franz diffusion cells. The apparent permeability coefficient (Papp) of BNsingle bondNLC gel was much higher (4.46-fold) than that of BN eye drops. Through the determination of corneal hydration levels, BNsingle bondNLC gel was confirmed that had no significant irritation to cornea.Ex vivoprecorneal retention experiments were carried out by a flow-through approach. The results indicated that the NLC-based hydrogel can prolong precorneal residence time. In conclusion, the hybrid NLC-based hydrogel has a promising potential for application in ocular drug delivery.