实心微针辅助酮洛芬贴片经皮给药的促透效果评价  

Evaluation of Penetration Promoting Effect of Solid Microneedle-Assisted Ketoprofen Patches Percutaneous Drug Delivery

作　　者：陈朴 方任华 江昌照 叶金翠 蒋秀梅 CHEN Pu;FANG Renhua;JIANG Changzhao;YE Jincui;JIANG Xiumei(Key Laboratory of Neuropsychiatric Drug Research of Zhejiang Province,Institute of Materia Medica,Hangzhou Medical College,Hangzhou,310013,China)

机构地区：[1]浙江省神经精神疾病药物研究重点实验室,杭州医学院,杭州310013

出　　处：《中国药学杂志》2024年第12期1135-1141,共7页Chinese Pharmaceutical Journal

基　　金：浙江省自然科学基金联合基金项目资助(LHDMZ22H300013);浙江省基础公益研究计划项目资助(LTGD23H300001);浙江省医药卫生科技项目资助(2023560486);浙江省中医药科技计划项目资助(2022ZB222,2023ZL357,2023017686)。

摘　　要：目的以药物酮洛芬为模型药物,研究并评价实心微针辅助透皮贴剂给药在体内、外的药物促透效果。方法采用大鼠皮肤渗透实验,考察微针的长度、预处理压力、预处理时间以及针型对酮洛芬的体外促透效果的影响;并研究了大鼠在体皮肤经不同微针预处理后,酮洛芬贴片于大鼠背部皮肤给药的药物动力学特征,评价其体内促透效果。结果离体皮肤渗透试验结果显示,经微针预处理后贴片的药物经皮渗透速率和渗透量显著提高(P<0.05),渗透时滞显著缩短(P<0.05),促透效果与微针预处理的压力、时间、微针长度与类型相关,在压力为1~7 N、时间1~5 min、针长200~300μm条件下,多次实验药物24 h的累积渗透量增加1.16~3.09倍,渗透时滞缩短0.20~2.50 h。根据大鼠体内药动学结果,当300μm滚轮微针预处理皮肤后ρ_(max)(10.86±0.80)μg·mL^(-1)和AUC_(0→t)(108.10±17.06)μg·h·mL^(-1)均显著大于对照组ρ_(max)(0.42±0.03)μg·mL^(-1)和AUC_(0→t)(7.46±0.98)μg·h·mL^(-1)(P<0.05),达峰时间(t_(max))亦显著快于对照组(P<0.05)。ρ_(max)和AUC_(0→t)分别提高25.9倍和14.5倍。结论实心微针预处理皮肤可显著提高酮洛芬贴片经大鼠皮肤的体外渗透和在体皮肤吸收,在体促透效果更显著。OBJECTIVE To investigate the penetration effect of solid microneedle in vivo and in vitro,the model drug ketoprofen was administered in the form of a patch.METHODS Using a rat skin penetration test,the effects of microneedle length,pre-treatment pressure,pre-treatment time,and types of needle on the penetration enhancement of ketoprofen in vitro were investigated.The pharmacokinetic characteristics of ketoprofen patches applied to the back of rats after different microneedle treatments were investigated,as well as the effect of the ketoprofen patch on promoting permeability in vivo.RESULTS In vitro,skin permeation tests revealed that after microneedle pretreatment,the permeation rate and permeation volume of the patch were significantly increased(P<0.05)and the permeation time lag was significantly shortened(P<0.05)after microneedle pretreatment,while the permeation promotion effect was related to the pressure,time,microneedle length and type of microneedle pretreatment.After microneedle pretreatment of the skin(pressure:1-7 N,time:1-5 min,microneedle length:200μm-300μm),the cumulative permeation amount of the experimental drug for 24 hours increased by 1.16-3.09 times,and the permeation delay decreases by 0.20-2.50 h.As the results of in vivo pharmacokinetic in rats,ρ_(max)(10.86±0.80)μg·mL^(-1)and AUC_(0→t)(108.10±17.06)μg·h·mL^(-1)after 300μm roller microneedle pretreatment of the skin,which were significantly greater than the controlρ_(max)(0.42±0.03)μg·mL^(-1)and AUC_(0→t)(7.46±0.98)μg·h·mL^(-1)(P<0.05).ρ_(max)and AUC_(0→t)were increased by 25.9 times and 15 times.CONCLUSION Solid microneedle pretreatment of skin significantly improves in vitro penetration and in vivo skin absorption of ketoprofen patches through rat skin,with a more significant promotion effect in vivo penetration.

关 键 词：微针 酮洛芬 经皮给药 药物动力学 高效液相色谱法 液相色谱-四极杆飞行时间质谱 

分 类 号：R944[医药卫生—药剂学]