Synthesis and properties of submicron albumin spheres

There has been considerable research into the use of human serum albumin microspheres as insoluble drug carriers for controlled delivery and sustained release of drugs. Albumin submicrospheres synthesized by methods reported to date are hydrophobic and require surfactants for preparation of injectable aqueous dispersions. Hydrophilic albumin microspheres have been recently synthesized in this laboratory and partially characterized but have been restricted in size to greater than 1 {dollar}mu{dollar}m.; A primary objective of this study was the development of a method for preparing hydrophilic albumin submicron spheres (submicrospheres). Round solid submicrospheres suitable for investigation of systemic administration were readily prepared by this method and their properties investigated.; Electron microscopy indicated that the synthesis is capable of producing submicrospheres in a wide size range (10 nm-1 {dollar}mu{dollar}m). A variety of soluble and particulate substances were incorporated into the spheres during synthesis, such as polyglutamic acid, magnetite grains, barium sulfate, and carboxymethyl cellulose, and were successfully entrapped during synthesis in a variety of concentrations.; The hydrophilic nature of the submicrospheres reported here allows the postsynthesis incorporation of high concentrations of drugs. For example, submicrospheres containing up to 48 wt% of adriamycin were synthesized. Submicrospheres containing other drugs were also prepared and drug release properties were measured in vitro by a static flow technique.; In vitro uptake of submicrospheres by rabbit blood cells and systemic clearance of isotope-labeled submicrospheres in rabbits were studied. A low level of uptake by white cells was observed in vitro and 98% of intravenously administered submicrospheres were removed from the circulation in two hours.; Hydrophilic albumin microspheres in the 1-20 {dollar}mu{dollar}m size range were also synthesized to study their biodegradation. Enzymatic degradation was examined with respect to the effect of size, enzyme concentration, and cross-link density on the rate and extent of degradation. The effects of size and cross-link density on soft tissue degradation were also studied in vivo following intramuscular and intratumoral injection in mice.; The results of this study indicate that albumin microspheres and submicrospheres have significant potential as drug carriers for localized delivery and sustained release of drugs.