Title:Improving Protein Stability and Controlling Protein Release by Adding Poly (Cyclohexane -1, 4 -Diyl Acetone Dimethylene Ketal) to PLGA Microspheres
Volume: 12
Issue: 6
Author(s): Chenhui Wang, Changhui Yu, Kongtong Yu, Lesheng Teng, Jiaxin Liu, Xuesong Wang, Fengying Sun and Youxin Li
Affiliation:
Keywords:
Biodegradable polymers, microspheres, PCADK, pH, PLGA, protein drug.
Abstract: The use of biodegradable polymers such as PLGA to encapsulate therapeutic proteins for
their controlled release has received tremendous interest. However, an acidic environment caused by
PLGA degradation productions leads to protein incomplete release and chemical degradation. The aim
of this study was to develop novel PCADK/PLGA microspheres to improve protein stability and release
behavior. Bovine serum albumin (BSA) incubated in PCADK and PLGA degradation products
was investigated using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), size
exclusion chromatography (SEC-HPLC), circular dichroism (CD) and fluorescence spectroscopy. Blended microspheres
of PCADK/PLGA were prepared in different ratios and the release behaviors of the microspheres and the protein stability
were then measured. The degradation properties of the microspheres and the pH inside the microspheres were systematically
investigated by scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM) to examine
the mechanism of autocatalytic degradation and protein stability. BSA was more stable in the presence of PCADK monomers
than it was in the presence of PLGA monomers, revealing that PCADK is highly compatible with this protein.
PCADK/PLGA microspheres were successfully prepared, and 2/8 was determined to be the optimal ratio. Further, 43% of
the BSA formed water-insoluble aggregates in the presence of PCADK/PLGA microspheres, compared with 57% for the
PLGA microspheres, demonstrating that the BSA encapsulated in PCADK/PLGA blended microspheres was more stable
than in PLGA microspheres. The PCADK/PLGA blended microspheres improved protein stability and release behavior,
providing a promising protein drug delivery system.
