Wet Sol-Gel Silica Microspheres for the Sustained Release of Human Growth Hormone

Sol-gel silica in the wet form formulated in the shape of microsphere was investigated for the controlled release of protein drugs and in particular human growth hormone (r-hGH). The influence of the gel SiO2 content on protein conformation, load and release rate was investigated. Protein fold upon gel embedment was measured by circular dichroism analysis and was found to be unaffected up to a concentration of SiO2 equal to 12% w/v, while minor loss of r-hGH a-helix occurred at higher silica concentration. Several r-hGH loaded microspheres containing 5, 8, 10, 12 and 15% SiO2 (w/v) were synthesized using a surfactant-free W/O pseudo-emulsion method, purposely selected to minimize the risk of protein unfolding. The amount of protein that can be incorporated in the polymer and is released in a controlled way was found to depend on the matrix silica content, varying form 0.6 mg to more than 5.3 mg/ml of wet gel for the 5% and 12-15% SiO2 formulations respectively. At low silica concentration, total release of r-hGH from microspheres occurs within 12 hours and it is mostly driven by diffusion through the gel pores. At higher SiO2 content, release is significantly slower and it is mostly dominated by polymer erosion with a time scale that varies between 100 and 150 hours depending on the formulation under investigation.