Preparation, characterization, and in vivo evaluation of levonorgestrel-loaded thermostable microneedles.

Abstract

To facilitate the storage and use of poly (lactic-co-glycolic acid) (PLGA)-based microneedles (MNs) in hot seasons and regions, thermally stable MNs loaded with levonorgestrel (LNG) were developed. Due to its good biocompatibility and high glass transition temperature (Tg), Hydroxypropyl methylcellulose (HPMC) was added to the PLGA-based MNs to increase thermal stability. MNs with HPMC exhibited excellent thermal stability at high temperatures. After the MNs has been applied to the skin for 10min, the backing layer of the MNs was dissolved by contact with the interstitial fluid of skin, which resulted in the separation of the MN tips from the backing layer. The MN tips were implanted intradermally and sustained-release LNG. Biodegradable polymers were used to encapsulate the LNG, providing long-acting contraception. The in vitro release rate of LNG from the MNs reached 72.78%-83.76% within 21days. In rats, the MNs maintained plasma concentrations of LNG above the human contraceptive level for 8-12days. In mice, the time required for complete degradation of the MN tips was 12-16days. MNs have excellent medication adherence due to the advantages of painlessness, minimally invasive, and self-administered. MNs can make long-acting contraceptives more readily available to humans.