Hollow hydroxyapatite microspheres as a device for controlled delivery of proteins

Hollow hydroxyapatite (HA) microspheres were prepared by reacting solid microspheres of Li(2)O-CaO-B(2)O(3) glass (106-150 microm) in K(2)HPO(4) solution, and evaluated as a controlled delivery device for a model protein, bovine serum albumin (BSA). Reaction of the glass microspheres for 2 days in 0.02 M K(2)HPO(4) solution (pH = 9) at 37°C resulted in the formation of biocompatible HA microspheres with a hollow core diameter equal to 0.6 the external diameter, high surface area (~100 m(2)/g), and a mesoporous shell wall (pore size ≈ 13 nm). After loading with a solution of BSA in phosphate-buffered saline (PBS) (5 mg BSA/ml), the release kinetics of BSA from the HA microspheres into a PBS medium were measured using a micro bicinchoninic acid (BCA) protein assay. Release of BSA initially increased linearly with time, but almost ceased after 24-48 h. Modification of the BSA release kinetics was achieved by modifying the microstructure of the as-prepared HA microspheres using a controlled heat treatment (1-24 h at 600-900°C). Sustained release of BSA was achieved over 7-14 days from HA microspheres heated for 5 h at 600°C. The amount of BSA released at a given time was dependent on the concentration of BSA initially loaded into the HA microspheres. These hollow HA microspheres could provide a novel inorganic device for controlled local delivery of proteins and drugs.