An Injectable Thermogel Containing Levonorgestrel for Long-Acting Contraception and Fertility Control of Animals.

Abstract

The demand of contraception and fertility control of animals is huge in livestock field and pet market. In this study, we suggest a formulation made up of an injectable and biodegradable thermogel for sustained delivery of levonorgestrel (LNG), a hormonal contraceptive, to realize the long-acting animal contraception. A thermogelling poly(lactic acid-co-glycolic acid)-poly(ethylene glycol)-poly(lactic acid-co-glycolic acid) (PLGA-PEG-PLGA) triblock copolymer was synthesized in a one-pot reaction. The micelles formed by the amphiphilic polymer carriers in water could serve as a reservoir for the solubilization of hydrophobic LNG molecules. The concentrated polymer aqueous solution exhibited a reversible sol-gel transition upon heating, and the incorporation of various amounts of LNG was found not to affect the thermogelation of the polymer/water system. In vitro release profiles showed that the entrapped LNG was sustainedly released from the thermogel matrix and the initial drug-loading amounts had a significant influence on the release kinetics of LNG. In vivo pharmacokinetic studies demonstrated that the use of PLGA-PEG-PLGA thermogel markedly extended the release of LNG after subcutaneous injection into SD rats. Consequently, this study revealed that the injectable PLGA-PEG-PLGA thermogel was a promising candidate for sustained delivery of LNG, and provided an attractive option for long-term contraception and fertility control of animals by a way of facile fabrication, easy administration and low expense.