Impact of terminal groups on PLGA degradation rate and their role in sustained release of cyproterone acetate.

Poly(lactic-co-glycolic acid) (PLGA) is the most commonly used commercially available polymeric pharmaceutical excipient for developing injectable long-acting release products. Its degradation rate is influenced by factors, such as molecular weight, the lactic/glycolic ratio (L/G ratio), and the nature of terminal groups. These variables impose challenges in achieving a precisely controlled release of loaded active compounds from finished PLGA-based formulations. This study investigated the impact of varying PLGA terminal groups on drug loading, encapsulation efficiencies, and drug release profiles in PLGA microspheres. We synthesized PLGA with four distinct terminal groups: carboxyl, n-hexyl, dodecyl, and hexadecyl, while keeping molecular weights and L/G ratios consistent to isolate the effects of the terminal groups on PLGA properties. Also, we examined how terminal groups influence the degradation behavior of PLGA microspheres and found that longer carbon chain lengths in the terminal groups resulted in a slower degradation rate. We have developed a novel method for analyzing terminal groups, enabling us to verify our synthesized products and to compare them against commercially available products. This method enhances the accuracy of our analyses and ensures the integrity of our product verification process. Additionally, we explored the underlying mechanism by which terminal groups affect the PLGA degradation. We then prepared four PLGA microspheres loaded with cyproterone acetate (CYA) through emulsification. The resulting microspheres exhibited consistent morphology, and a volume mean diameter of 9 to 11 µm,a drug loading rate of about 10% and an encapsulation efficiency of approximately 97%. The results of in vitro release experiments showed that CYA release from all microspheres could be sustained for up to two months with a recovery rate reaching 100%. Meanwhile, we investigated the mechanism of loaded drug release from PLGA microspheres with different terminal groups and elucidated how the degradation of PLGA influences the release profile of loaded drugs. The insights gained from this study will enhance the understanding of PLGA degradation and the mechanisms underlying the release of loaded actives from PLGA microspheres. Furthermore, the modification of terminal groups has the potential to support the development of advanced pharmaceutical excipients.