BIOTEK has developed a new process which uses calcium sulfate to make injectable biodegradable microspheres and microcapsules well suited for depot delivery of water soluble drugs such as peptides and proteins. Preliminary testing has shown that butyrylcholinesterase can be incorporated and released in active form, and recent improvements have made possible routine preparation of injectable 75 - 100 microm microspheres in high yield. The proposed Phase I work will study the effect of variations in composition, processing, loading and hydrophobic treatment on dissolution and delivery. The emphasis in Phase I will be on elucidating the mechanisms by which protein is held and released, and the program includes a study of protein distribution inside microspheres based on two techniques: silver staining combined with Energy Dispersive X- Ray Spectroscopy and controlled surface abrasion combined with protein analysis of the removal material. Phase II will use the data from Phase I to develop an injectable microsphere depot for a medicinal protein such as human growth hormone and will then pursue product development through demonstration of reproducibility, prototype manufacturing, quality assessment, stability testing, IND submission, and an initial human clinical study.
The new porous calcium sulfate microspheres are intended for eventual development into a generic protein depot delivery system in which empty microspheres could be manufactured at one facility and then distribute to other facilities for loading with proprietary protein drugs using mild processing conditions unlikely to lead to denaturation or loss of activity.
