Preparation and evaluation of injectable microsphere formulation for longer sustained release of donepezil

by Selleckchem | Mar 23 2023

In this study, donepezil-loaded PLGA and PLA microspheres (Dp-PLGA-M/Dp-PLA-M) and Dp-PLA-M wrapped in a polyethylene glycol-b-polycaprolactone (PC) hydrogel (Dp-PLA-M/PC) were prepared to reduce the dosing frequency of injections to treat Alzheimer's disease patients. Dp-PLGA-M and Dp-PLA-M with a uniform particle size distribution were repeatably fabricated in nearly quantitative yield and with high encapsulated Dp yields using an ultrasonic atomizer. The injectability and in vitro and in vivo Dp release, biodegradation, and inflammatory response elicited by the Dp-PLGA-M, Dp-PLA-M, and Dp-PLA-M/PC formulations were then compared. All injectable formulations showed good injectability with ease of injection, even flow, and no clogging using a syringe needle under 21-G. The injections required a force of <1 N. According to the biodegradation rate of micro-CT, GPC and NMR analyses, the biodegradation of Dp-PLA-M was slower than that of Dp-PLGA-M, and the biodegradation rate of Dp-PLA-M/PC was also slower. In the Dp release experiment, Dp-PLA-M sustained Dp for longer compared with Dp-PLGA-M. Dp-PLA-M/PC exhibited a longer sustained release pattern of two months. In vivo bioavailability of Dp-PLA-M/PC was almost 1.4 times higher than that of Dp-PLA-M and 1.9 times higher than that of Dp-PLGA-M. The variations in the Dp release patterns of Dp-PLGA-M and Dp-PLA-M were explained by differences in the degradation rates of PLGA and PLA. The sustained release of Dp by Dp-PLA-M/PC was attributed to the fact that the PC hydrogel served as a wrapping matrix for Dp-PLA-M, which could slow down the biodegradation of PLA-M, thus delaying the release of Dp from Dp-PLA-M. Dp-PLGA-M induced a higher inflammatory response compared to Dp-PLA-M/PC, suggesting that the rapid degradation of PLGA triggered a strong inflammatory response. In conclusion, Dp-PLA-M/PC is a promising injectable Dp formulation that could be used to reduce the dosing frequency of Dp injections.

Comments：

The study investigated the development of an injectable formulation for donepezil (Dp) to treat Alzheimer's disease patients. The formulation included Dp-loaded microspheres made of polylactic acid (PLA) or poly(lactic-co-glycolic acid) (PLGA), and a PLA microsphere wrapped in a hydrogel made of polyethylene glycol-b-polycaprolactone (PC) to reduce the dosing frequency of injections. The study compared the injectability, in vitro and in vivo release of Dp, biodegradation, and inflammatory response of the formulations.

The study found that all injectable formulations had good injectability, and the injections required a force of less than 1 N. Dp-PLA-M sustained Dp release for a longer duration than Dp-PLGA-M, and Dp-PLA-M/PC exhibited a sustained release pattern for two months. The in vivo bioavailability of Dp-PLA-M/PC was higher than Dp-PLA-M and Dp-PLGA-M, indicating its effectiveness in reducing the dosing frequency. The slower biodegradation rate of PLA-M and Dp-PLA-M/PC compared to PLGA-M was attributed to the PC hydrogel, which acted as a wrapping matrix for Dp-PLA-M, thus delaying the release of Dp.

The study also found that Dp-PLGA-M induced a higher inflammatory response compared to Dp-PLA-M/PC, indicating that the rapid degradation of PLGA triggered a strong inflammatory response. In conclusion, the study suggests that Dp-PLA-M/PC is a promising injectable formulation for Dp that could reduce the dosing frequency of injections and improve patient compliance.