Intradermal Implantable PLGA Microneedles for Etonogestrel Sustained Release.

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 AUC0→48h only accounted for 37.8% of AUC0→∞. Therefore, this developed intradermal implantable MNs could provide a minimally invasive sustained-release system suitable for self-administration.