Protein delivery using mesoporous ceramic/ polymer hybrid
Date of Issue2011
School of Materials Science and Engineering
Mesostructured materials of high specific surface area and pore volume were hypothesized to have the ability to encapsulate higher amount of proteins in the delivery systems. Hence, high surface area of mesostructured calcium phosphates (MCP) and mesoporous bioactive glasses (MBG) had been successfully synthesized for the protein adsorption study. The adsorption of Lysozyme (LSZ) and Bovine serum albumin (BSA) molecules onto MCP or MBG was governed by surface area of mesostructured materials, electrostatic interaction between proteins and mesostructured materials as well as the conformation stability of proteins. The initial in vitro protein release rate was affected by the amount of protein being loaded. The secondary structure of the proteins was preserved after release. MCP and MBG powders of different weight ratios were further being incorporated into the PLGA system to investigate the in vitro degradation and protein release behavior. The presence of MCP and MBG (> 10 wt%) increased the bulk hydrophilicity of the PLGA matrix and neutralized the acidic environment caused by the oligomers and monomers degraded from PLGA. As a result, the in vitro degradation of PLGA film was retarded without rapid increase of buffer absorption and mass loss. The mid phase degradation of the composite system was competed between the buffering effect of the inorganic bioceramics, leaching of the MCP or MBG and the dissolution of acidic degradation products. The composite release system exhibited multiphasic profile. The initial release rate of the composite film was controlled by the amount of protein adsorbed on the inorganic materials. The higher amount of inorganic samples (i.e. MCP or MBG) could lengthen the mid time phase diffusion process because the inorganic samples could neutralize the pH environment of the matrix and prevent rapid mass loss and buffer absorption to take place. The bioactivity of protein released from PLGA film showed that there was a peak shift of the negative ellipticity (6) from 208 nm to 216 nm which indicated a switch from a-helix to P-sheet conformation was induced. As a result, the bioactivity of protein BSA and LSZ released from PLGA film was affected. Several characterization techniques including XRD, FTIR, TGA, nitrogen adsorption analysis, FESEM and TEM were conducted on the surface area optimization of the mesostructured materials. The in vitro degradation and the protein adsorption studies were examined using GPC, UV-Vis spectrophotometer, nanosizer and CD spectropolarimeter.
Nanyang Technological University