聚丙烯酸树脂蒙脱石镶嵌盐酸倍他洛尔纳米粒滴眼液的眼表代谢及体外刺激性评价  

Evaluation of ocular surface metabolism and in vitro irritation of polyacrylic resin with montmorillonite embedding betaxolol hydrochloride nanoparticles

作　　者：许慧慧 韩鑫玥 刘朔 赵雅文 李华梅 刘晗雨 杨帆 陈燕忠 潘育方 侯冬枝 XU Huihui;HAN Xinyue;ZHAO Yawen;LIU Shuo;LI Huamei;LIU Hanyu;YANG Fan;CHEN Yanzhong;PAN Yufang;HOU Dongzhi(School of Pharmacy,Guangdong Pharmaceutical University,Guangdong Provincial Engineering Center of Topical Precise Drug Delivery System/Guangdong Provincial Key Laboratory of Advanced Drug Delivery System,Guangzhou 510006,China)

机构地区：[1]广东药科大学药学院/广东省局部精准递药制剂工程技术研究中心/广东省药物新剂型重点实验室,广东广州510006

出　　处：《广东药科大学学报》2021年第6期1-6,共6页Journal of Guangdong Pharmaceutical University

基　　金：广东省医学科学技术研究项目(A2016275);广东药科大学大学生创新创业训练计划项目(S202010573025)。

摘　　要：目的以盐酸倍他洛尔(BH)为模型药物,通过聚丙烯酸树脂(ED)和蒙脱石(Mt)的联合使用,制备可调节药物释放的聚丙烯酸树脂蒙脱石镶嵌盐酸倍他洛尔纳米粒(ED-Mt-BH NPs)用于眼部给药,考察此新型给药系统的眼表代谢能力和体外刺激性。方法采用O/W溶剂挥发法制备ED-Mt-BH NPs并初步评估其制剂学性质;通过动态透析法考察体外释放行为;以滤纸条法进行泪液消除试验评价眼表代谢能力,进一步评估角膜前滞留能力;兔红细胞溶血试验和MTT细胞毒试验对该眼部给药系统的刺激性进行综合考察。结果 ED-Mt-BH NPs粒径为(88.3±3.6)nm,呈正电性,包封率和载药量分别为(76.42±0.11)%和(4.97±0.15)%,TEM图像显示颗粒圆整,pH值和渗透压均符合2020年版《中国药典》要求;体外释放试验显示释放速度明显平缓于BH溶液;泪液消除试验表明ED-Mt-BH NPs的生物利用度和平均滞留时间分别是BH溶液的1.88倍和1.54倍;ED-Mt-BH NPs和PBS以不同比例混合后的溶血率均小于5%,MTT细胞毒性试验表明纳米粒对药物BH的有效包裹可显著降低BH的毒性。结论 ED-Mt-BH NPs能有效延长盐酸倍他洛尔的释放时间,增加该药物在眼表的滞留能力且生物相容性良好。Objective The polyacrylic resin montmorillonite nanoparticles(ED-Mt-BH NPs) was prepared for ocular drug delivery with betaolol hydrochloride(BH) as a model drug by the combined use of polyacrylic resin(ED) and montmorillonite(Mt). The ocular surface metabolism and in vitro irritation of this new drug delivery system were investigated. Methods ED-Mt-BH NPs were prepared by the oil-in-water solvent evaporation method, and their pharmaceutical properties were preliminarily evaluated. The release behavior in vitro of the nano-drug delivery system was investigated by thin-film dialysis, and the tear strip elimination test was carried out by the filter paper strip method to evaluate its ocular surface metabolic capacity and further evaluate its precorneal retention capacity. The rabbit erythrocyte hemolysis test and MTT cytotoxicity test comprehensively evaluated the irritation of the ocular drug delivery system. Results The particle size of the nanoparticles was(88.3±3.6) nm, which was positively charged. The encapsulation efficiency and drug loading were(76.42±0.11)%and(4.97±0.15)%, respectively. The TEM electron microscope showed that the particles were round, and the p H value and osmotic pressure were in line with the 2020 edition Chinese Pharmacopoeia requirements. The release rate of ED-Mt-BH NPs was significantly slower than that of the BH solution. Tear elimination test showed that the bioavailability and average residence time of ED-Mt-BH NPs eye drops were 1.88 times and 1.54 times that of BH solution. The hemolysis rate of ED-Mt-BH NPs and PBS mixed in different proportions was less than 5%. MTT cytotoxicity experiments showed that the effective encapsulation of nanoparticles on the BH could significantly reduce the toxicity of BH. Conclusion ED-Mt-BH NPs can effectively prolong the time of drug release, increase drug retention on the ocular surface and have good biocompatibility.

关 键 词：盐酸倍他洛尔 聚丙烯酸树脂 纳米粒 溶血 MTT法 细胞毒性 

分 类 号：R944[医药卫生—药剂学]