王景雁;张艳菊;张欢;赵文文;刘宗洋;王海伦;梅冬;吴清;
WANG Jing-yan;ZHANG Yan-ju;ZHANG Huan;ZHAO Wen-wen;LIU Zong-yang;WANG Hai-lun;MEI Dong;WU Qing;National Center for Children′s Health, Beijing Children′s Hospital, Capital Medical University;School of Chinese Materia Medica, Beijing University of Chinese Medicine;

• 1:国家儿童医学中心首都医科大学附属北京儿童医院
• 2:北京中医药大学中药学院

摘要(Abstract)：

该文拟设计并制备近红外响应型盐酸青藤碱贮库微针，通过对其机械力学性质及体外释放特征的表征，以评价该类型微针提高载药量和经皮吸收的可行性。选择盐酸青藤碱为模型药物，以单甲氧基聚乙二醇-聚己内酯嵌段共聚物(MPEG-PCL)和吲哚菁绿(ICG)为两亲性嵌段共聚物和光诱导剂，制备近红外响应型纳米粒，并基于气泡微针(bubble microneedle)制备原理，设计并制备近红外响应型盐酸青藤碱贮库微针；通过测定微针形态、长度、力学性能、皮肤刺入特征等表征近红外响应型盐酸青藤碱贮库微针制剂特征，同时，采用体外释放试验评价贮库式微针的释药性能。结果显示，所制备的盐酸青藤碱微针呈圆锥形，暴露针尖高度约650μm,每平方厘米可容纳约0.5 mg药物，且该类型微针机械力学性能和皮肤刺入能力良好，体外释放实验显示，该微针24 h单位面积累积释放量和释放率分别为825.61μg·cm^(-2)和74.3%,其释放动力学符合一级动力学模型。该研究初步证明贮库式微针可有效提高微针的载药量，且机械性能和释放性能良好。
The present study designed and prepared near-infrared responsive sinomenine hydrochloride(SIN) reservoir microneedles and evaluated the feasibility of this type of microneedles in increasing the drug loading and transdermal absorption by characterizing their mechanical properties and in vitro release characteristics.SIN was selected as the model drug, and methoxy poly(ethylene glycol) poly(caprolactone)(mPEG-PCL) copolymers and indocyanine green(ICG) were employed as amphiphilic block copolymers and light inductor to prepare near-infrared responsive nanoparticles.Based on the preparation principle of bubble microneedles, near-infrared responsive SIN reservoir microneedles were designed and prepared.The features of the near-infrared responsive SIN reservoir microneedles were characterized by measuring the morphology, length, mechanical properties, and skin penetration of microneedles.Meanwhile, the drug release performance of reservoir microneedles was evaluated by in vitro release assay.The results showed that the prepared SIN microneedles were conical, with an exposed tip height of about 650 μm.Each needle could load about 0.5 mg of drugs per square centi-meter, and this type of microneedle showed good mechanical properties and performance in skin penetration.The results of the in vitro release assay showed that the 24 h cumulative release per unit area and release rate of the microneedle were 825.61 μg·cm(-2)和74.3%,其释放动力学符合一级动力学模型。该研究初步证明贮库式微针可有效提高微针的载药量，且机械性能和释放性能良好。
The present study designed and prepared near-infrared responsive sinomenine hydrochloride(SIN) reservoir microneedles and evaluated the feasibility of this type of microneedles in increasing the drug loading and transdermal absorption by characterizing their mechanical properties and in vitro release characteristics.SIN was selected as the model drug, and methoxy poly(ethylene glycol) poly(caprolactone)(mPEG-PCL) copolymers and indocyanine green(ICG) were employed as amphiphilic block copolymers and light inductor to prepare near-infrared responsive nanoparticles.Based on the preparation principle of bubble microneedles, near-infrared responsive SIN reservoir microneedles were designed and prepared.The features of the near-infrared responsive SIN reservoir microneedles were characterized by measuring the morphology, length, mechanical properties, and skin penetration of microneedles.Meanwhile, the drug release performance of reservoir microneedles was evaluated by in vitro release assay.The results showed that the prepared SIN microneedles were conical, with an exposed tip height of about 650 μm.Each needle could load about 0.5 mg of drugs per square centi-meter, and this type of microneedle showed good mechanical properties and performance in skin penetration.The results of the in vitro release assay showed that the 24 h cumulative release per unit area and release rate of the microneedle were 825.61 μg·cm^(-2) and 74.3%, respectively, which indicated that its release kinetics was in line with the first-order kinetic model.This study preliminarily proved that the reservoir microneedle could effectively increase the drug loading with good mechanical properties and release perfor-mance.

关键词(KeyWords)： 盐酸青藤碱;经皮吸收;微针;近红外响应;单甲氧基聚乙二醇-聚己内酯嵌段共聚物
sinomenine hydrochloride;transdermal absorption;microneedle;near-infrared response;methoxy poly(ethylene glycol) poly(caprolactone)(mPEG-PCL) copolymer

Abstract:

Keywords:

基金项目(Foundation): 北京市自然科学基金项目(7192109);; 北京市医院管理中心“青苗”计划项目(QMS20201201);; 北京市优秀人才项目(2018000021469G279);; 国家呼吸系统疾病临床医学研究中心呼吸专项(HXZX-202107)

作者(Authors): 王景雁;张艳菊;张欢;赵文文;刘宗洋;王海伦;梅冬;吴清;
WANG Jing-yan;ZHANG Yan-ju;ZHANG Huan;ZHAO Wen-wen;LIU Zong-yang;WANG Hai-lun;MEI Dong;WU Qing;National Center for Children′s Health, Beijing Children′s Hospital, Capital Medical University;School of Chinese Materia Medica, Beijing University of Chinese Medicine;

DOI: 10.19540/j.cnki.cjcmm.20220411.301

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