Key Laboratory of Photochemical Conversion and Optoelectronic Materials, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing 100190, China; Yantai Key Laboratory of Nanomedicine & Advanced Preparations, Yantai Institute of Materia Medica, Shandong 264000, China.
Key Laboratory of Photochemical Conversion and Optoelectronic Materials, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing 100190, China; Beijing CAS Microneedle Technology Ltd., Beijing 102600, China.
J Pharm Sci. 2020 Jun;109(6):1958-1966. doi: 10.1016/j.xphs.2020.02.009. Epub 2020 Feb 19.
This study reported novel long-acting microneedles (MNs) that can be implanted into the skin in situ quickly. It was prepared to entrap a model drug in the biodegradable poly(lactide-co-glycolide) (PLGA) needle tips by a controllable casting-mold technique, avoiding the effect of high temperature melting the drug stability. The third-generation progesterone etonogestrel (ENG) was selected as the model drug. A new preparing method of MNs was proposed by using N-methyl pyrrolidinone as a solvent for needle tip matrix with good biocompatibility and safety. After solidified at 70°C for 4 h, the needle tips were strong enough to puncture the skin. ENG could crystallize uniformly in needle tips, observed by a polarizing microscope. The intradermal implantation ratio of the MNs was affected by the parameters of needle shape and needle spacing. With optimization of MN formulations, the drug loading capacity was 153.0 ± 13.5 μg, and the drug utilization rate was up to 92.6 ± 8.1%. In rats, the pharmacokinetic study of the implantable MNs showed that the plasma ENG level could be detectable until 336 h and the AUC only accounted for 37.8% of AUC. Therefore, this developed intradermal implantable MNs could provide a minimally invasive sustained-release system suitable for self-administration.
本研究报道了一种新型的长效微针（MNs），可以快速原位植入皮肤。它是通过可控的浇铸模具技术制备的，将模型药物包埋在可生物降解的聚（乳酸-共-乙醇酸）（PLGA）针尖端内，避免了高温对药物稳定性的影响。第三代孕激素左炔诺孕酮（ENG）被选为模型药物。提出了一种新的 MNs 制备方法，使用 N-甲基吡咯烷酮作为具有良好生物相容性和安全性的针尖基质溶剂。在 70°C 下固化 4 小时后，针尖足以刺穿皮肤。ENG 可以在针尖中均匀结晶，通过偏光显微镜观察到。MNs 的皮内植入比例受针尖形状和针尖间距等参数的影响。通过对 MN 配方进行优化，载药量达到 153.0±13.5μg，药物利用率高达 92.6±8.1%。在大鼠中，植入式 MNs 的药代动力学研究表明，植入后可检测到 ENG 水平至 336 小时，AUC 仅占 AUC 的 37.8%。因此，这种开发的皮内植入式 MNs 可以提供一种微创的持续释放系统，适合自我给药。
