The effect of polymer blends on initial release regulation and in vitro-in vivo relationship of peptides loaded PLGA-Hydrogel Microspheres

[Display omitted] •Overcame the lag time issue which could reduce the limitation of PLGA-Hydrogel-Microspheres in developing long-acting-release products of peptides.•Proposed and established the segmented phases IVIVR for the first time which solve the challenges caused by multiphasic release profiles of PLGA microspheres. The aim of this study was to resolve the lag time problem for peptides loaded PLGA-Hydrogel Microspheres (PLGA-gel-Ms) by blending low molecular PLGA (Mw. 1 kDa) into PLGA (Mw. 10 kDa) as an intrinsic porogen, and then assess the in vitro-in vivo relationship (IVIVR). Here, Goserelin acetate (GOS) was chosen as the model peptides. When compared to additional types of porogen, the intrinsic porogen avoided impurities remaining and protected the bioactivities of the peptides. By adding 10% PLGA (Mw. 1 kDa), the lag time was eliminated both in vitro and in vivo with a desirable EE (97.04% ± 0.51%). The release mechanisms were found to be: a) initial GOS release mainly controlled by pores diffusion and b) autocatalysis of PLGA (Mw. 1 kDa) which increased the quantity of aqueous pores, as revealed by SEM images. To solve the challenges caused by multiphasic release profiles, for the first time the Segmented phases IVIVR were proposed and developed, and showed improved linear fitting effects and supported the proposed release mechanisms. The application of PLGA blends could provide a new insight into PLGA microsphere initial release rate regulation.