Incorporation and release of macromolecules from biodegradable polymer vehicles
The initial objective of this work was to evaluate and introduce fabrication techniques based on W/O/W double emulsion and O/W single emulsion systems with solvent evaporation for the incorporation of a surrogate macromolecule (BSA) into microspheres and microcapsules fabricated using P(HB-HV), PEA and their blends. Biodegradation, expressed as changes in the gross and ultrastructural morphology of BSA loaded microparticulates with time was monitored using SEM concomitant with BSA release. Spherical microparticulates were successfully fabricated using both the W/O/W and O/W emulsion systems. Both microspheres and microcapsules released BSA over a period of 24 to 26 days. BSA release from P(HB0HB)20% PCL 11 microcapsules increased steadily with time, while BSA release from all other microparticulates was characterised by an initial lag phase followed by exponential release lasting 6-11 days. Microcapsules were found to biodegrade more rapidly than microspheres fabricated from the same polymer. The incubation of microparticulates in newborn calf serum, synthetic gastric juice and pancreatin solution showed that microspheres and microcapsules were susceptible to enzymatic biodegradation. The in vitro incubation of microparticulates in Hank's buffer demonstrated limited biodegradation of microspheres and microcapsules by simple hydrolysis. BSA release was thought to occur as a result of the macromolecule diffusing through either inherent micropores or via pores and channels generated in situ by previously dissolved BSA. However, in all cases, irrespective of percentage loading or fabrication polymer, low encapsulation efficiencies were obtained with W/O/W and O/W techniques (4.20.9%-15.50.5%, n=3), thus restricting the use of these techniques for the generation of microparticulate sustained drug delivery devices. (DX 187, 341).