Biodegradable cross-linked starch/protein microcapsules containing proteinase inhibitor for oral protein administration

The objective of this study is to demonstrate the feasibility of microcapsu les containing a protein and a proteinase inhibitor in order to allow the o ral administration of proteic or peptidic drug. Starch/bovine serum albumin mixed-walled microcapsules were prepared using interfacial cross-linking w ith terephthaloyl chloride. The microcapsules were loaded with native or am ino-protected aprotinin by incorporating protease inhibitors in the aqueous phase during the cross-linking process. Microcapsules can be degraded in t he presence of alpha-amylase. The influence of the formulation parameters o n the in vitro release of the inhibitor activity and the protein was studie d. The protective effect of microcapsules with aprotinin for bovine serum a lbumin was revealed in vitro. The presence of the native bovine serum album in was demonstrated after incubation of the microcapsules with aprotinin in a mixture of alpha-amylase (5.4 U/ml) and trypsin (900 spectrophotometric BAEE units/ml) for 3 h at 37 degrees C, whereas the protein was completely degraded in the release medium of the microcapsules without aprotinin. (C) 1999 Elsevier Science B.V. All rights reserved.