Maintaining bioactivity of NGF for controlled release from PLGA using PEG

The goal of this work was to investigate methods to retain bioactivity of nerve growth factor (NGF) after encapsulation in poly(lactic-co-glycolic acid) (PLGA) discs for controlled release. Poly(ethylene glycol) (PEG) was chosen as a porogen not only to control the release rate of NGF but also because it has been used to help maintain bioactivity of molecules in organic solvents. NGF and PEG were encapsulated in PLGA via standard dissolution-evaporation techniques with methylene chloride as the solvent. Morita et al. (Pharm Res 2000; 17:1367-1373) indicated that colyophilization of PEG and bioactive factors before exposure to organic solvents increased the retention of bioactivity. Therefore, various PEG:NGF mass ratios were colyophilized before encapsulation within PLGA to examine retained activity of NGF. When PEG was not colyophilized before encapsulation, NGF activity was lost during the fabrication process. In contrast, colyophilization of PEG and NGF supported retention of NGF activity during the entire fabrication process. The amount of PEG encapsulated was the dominating factor in the rate of NGF release regardless of the fabrication method. These results demonstrate the usefulness of PEG in both acting as a porogen to modulate release and aiding in the retention of activity of NGF. This process may be extended to other methods to enhance activity of growth factors after exposure to organic solvents.