Investigation of mathematical models based on diffusion control release for Paclitaxel from in-situ forming PLGA microspheres containing HSA microparticles

摘要

Paclitaxel-loaded poly(lactic acid-co-glycolic acid) (PLGA) microspheres containing different portions of human serum albumin microparticles (mHSA) were prepared via an in situ forming method. The low solubility of Paclitaxel and presence of an external oil phase around the in situ-formed microspheres were investigated with the mathematical models based on the diffusion-control release. The release data were fitted with diffusion-based semi-empirical models including Ritger-Peppas, Weibull and Peppas-Sahlin models, and a theoretical model obtained from Fick's second law. The release rate constants, release exponent and average drug diffusion coefficients microspheres were calculated and their variations with PLGA molecular weight and microparticles were established. Results showed good accordance between experimental and theoretical values. Besides, incorporation of mHSA within microspheres decreased the Paclitaxel diffusion. Result of docking studies showed that the binding site of mHSA sequences including HIS242 and ARG114 have more significant interaction with paclitaxel, but no significant interaction between PLGA and paclitaxel.