Intradermal Implantable PLGA Microneedles for Etonogestrel Sustained Release

Meilin He; Guozhong Yang; Xiaoyu Zhao; Suohui Zhang; Yunhua Gao

doi:10.1016/j.xphs.2020.02.009

Intradermal Implantable PLGA Microneedles for Etonogestrel Sustained Release

J Pharm Sci. 2020 Jun;109(6):1958-1966. doi: 10.1016/j.xphs.2020.02.009. Epub 2020 Feb 19.

Authors

Meilin He¹, Guozhong Yang², Xiaoyu Zhao³, Suohui Zhang⁴, Yunhua Gao⁵

Affiliations

¹ 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.
² 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.
³ Key Laboratory of Photochemical Conversion and Optoelectronic Materials, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing 100190, China.
⁴ 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. Electronic address: suohuizhang@mail.ipc.ac.cn.
⁵ 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; University of Chinese Academy of Sciences, Beijing 100049, China. Electronic address: yhgao@mail.ipc.ac.cn.

PMID: 32084376
DOI: 10.1016/j.xphs.2020.02.009

Abstract

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_0→48h only accounted for 37.8% of AUC_0→∞. Therefore, this developed intradermal implantable MNs could provide a minimally invasive sustained-release system suitable for self-administration.

Keywords: etonogestrel; implantable microneedles; intradermal delivery; sustained release.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Administration, Cutaneous
Animals
Delayed-Action Preparations
Desogestrel*
Drug Delivery Systems
Needles*
Rats

Substances

Delayed-Action Preparations
etonogestrel
Desogestrel