温敏型盐酸青藤碱贮库式微针的制备及体内外评价  

Preparation and in vitro-in vivo evaluation of temperature-sensitive sinomenine hydrochloride reservoir microneedles

作　　者：王景雁 邓莉莉 陈佳佳 吴清[2] WANG Jingyan;DENG Lili;CHEN Jiajia;WU Qing(College of Health Industry,Sichuan Tourism University,Chengdu 610100,China;School of Chinese Materia Medica,Beijing University of Chinese Medicine,Beijing 102488,China)

机构地区：[1]四川旅游学院大健康产业学院,成都610100 [2]北京中医药大学中药学院

出　　处：《北京中医药大学学报》2024年第7期1025-1033,共9页Journal of Beijing University of Traditional Chinese Medicine

基　　金：国家自然科学基金项目(No.81473365);四川旅游学院自然科学重点项目(No.2023SCTUZD05);四川旅游学院专项科研项目(No.2023SCTUBSZK08)。

摘　　要：目的利用气泡微针技术及温敏型材料设计制备温敏型贮库式微针,探讨解决微针在中药外用制剂存在“载药量低”问题的可行性。方法首先,以盐酸青藤碱为模型药物,将药物与温敏型材料N-异丙基丙烯酰胺浇筑入由壳聚糖形成的气泡微针空腔中,通过定位固化等工艺,制备具有针体、定位层、基底层和药物贮库4个部分功能结构的温敏型贮库式微针;其次,对所制备的微针载药量、尺寸、力学、皮肤穿刺等载药能力和机械性能进行表征;最后,分别采用Franz扩散仪和经皮微渗析技术,评估该贮库式微针的体外和在体释药行为特征。结果所制备的温敏型贮库式微针载药量可达5.76 mg/cm^(2),暴露针尖呈圆锥型,高度约为650μm,且具良好机械强度和皮肤穿刺能力;体外释放试验显示,该微针在皮肤模拟温度条件下,可较大程度地释放针体内药物,并呈扩散和骨架溶蚀的释药特征;在体经皮渗透试验显示,相较于常规外用制剂,该贮库式微针可快速且明显促进药物的经皮吸收。结论该研究初步表明利用温敏型材料和气泡微针技术所制备的贮库式微针能明显提高微针载药量,并仍保持微针“微创”的作用优势。Objective This paper focuses on the manufacturing technique of bubble microneedles and temperature-sensitive materials in order to design and prepare a temperature-sensitive reservoir microneedle.The objective is to evaluate the feasibility of addressing the issue of low drug load in traditional Chinese medicine(TCM)external preparations using microneedles.Methods The study involved the utilization of sinomenine hydrochloride as the model drug.The drug,along with the temperature-sensitive material N-isopropylacrylamide,was filled into the cavity of the bubble microneedle made from chitosan.Through positioning and curing processes,a temperature-sensitive sinomenine hydrochloride reservoir microneedle was prepared.The microneedle consisted of a needle body,a positioning layer,a basal layer,and a drug reservoir.The drug load,size,length,mechanical properties,and puncture ability of the prepared reservoir microneedle were measured to characterize and evaluate its drug load and mechanical properties.In addition,the in vitro release characteristics of the microneedles were determined using Franz diffusion cells,while the in vivo release characteristics were evaluated using the percutaneous microdialysis technique.Results The research result demonstrated that the prepared temperature-sensitive reservoir microneedle had a drug load of approximately 5.76 mg/cm^(2).The exposed needle tip had a conical shape with a height of around 650μm,exhibiting good mechanical strength and skin puncture ability.The in vitro release tests showed that the microneedle could simulate the temperature of the skin and release the drug in a controlled and gradual manner,displaying characteristics of diffusion and dissolution of the skeleton.Furthermore,compared to conventional external preparations,the reservoir microneedles significantly enhanced transdermal permeation of the drug in the in vivo percutaneous studies.Conclusion The study demonstrated that reservoir-type microneedles prepared using temperature-sensitive materials and bubble mic

关 键 词：贮库式微针 经皮吸收 N-异丙基丙烯酰胺 盐酸青藤碱 

分 类 号：R283[医药卫生—中药学]