Preparation and in vivo evaluation of PCADK/PLGA microspheres for improving stability and efficacy of rhGH

The goal of this research is to prepare poly(cyclohexane-1,4 diyl acetone dimethylene ketal) (PCADK)/poly(d,l-lactide-co-glycolide) (PLGA) blend microspheres loaded with recombinant human growth hormone (rhGH). The effect of PCADK degradation products on the structural integrity, secondary and tertiary structure and pharmacodynamics of rhGH was evaluated by native-polyacrylamide gel electrophoresis (Native-PAGE), size-exclusion high performance liquid chromatography (SEC-HPLC), circular dichroism (CD), fluorescence spectroscopy and in hypophysectomized rat models. Compared with PLGA degradation products, rhGH was found to be more stable in the presence of PCADK degradation products. PCADK/PLGA blend microspheres were then prepared and the morphology, encapsulation efficiency, release behavior and rhGH stability were investigated. PCADK/PLGA microspheres had regular shapes and smooth surfaces when the proportion of PCADK was less than 50%. The late-releasable amount of rhGH in PCADK/PLGA microspheres was greater than that in PLGA microspheres. In addition, the PCADK/PLGA microspheres showed larger AUC and improved therapeutic effects on rats than PLGA microspheres. Furthermore, the pH inside the microspheres was detected by CLSM to explain the improved rhGH stability in the PCADK/PLGA microspheres. In conclusion, PCADK/PLGA blend microspheres showed potential to improve rhGH stability and the efficacy of sustained-release of rhGH compared with PLGA microspheres.

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