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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Improved activity of a new angiotensin receptor antagonist by an injectable spray-dried polymer microsphere preparation.

PURPOSE: To characterize and evaluate in vitro and in vivo the release mechanisms involved in spray-dried biodegradable microspheres having different Poly(D,L-lactide) blend formulations and containing an antihypertensive drug (L-158,809). METHODS: Microspheres and blended polymers were characterized by DSC, SEM, confocal laser microscopy and size analysis. In vitro release studies were evaluated by using microspheres made from various blends of high and low molecular weight polymer. In vivo studies were evaluated by L-158,809 antagonist AT1 function versus the shift of the normal dose-response curve of blood pressure induced by Angiotensine II. RESULTS: The average yield of L-158,809 microspheres (10% (w/w)) was 95% of the theoretical loading. The average diameter of the microspheres was from 1 to 3 micrometers. In all release experiments, a significant burst effect (< 15%) was observed followed by a near zero-order release kinetics. In vivo studies with two different formulations show a strong shift of angiotensin II dose-response curve. CONCLUSIONS: The release kinetics and photomicrographs suggest that the system is best described as a multi-parameter controlled released system in which the drug is molecularly dispersed. In vivo results demonstrating the controlled release of L-158,809.[1]


  1. Improved activity of a new angiotensin receptor antagonist by an injectable spray-dried polymer microsphere preparation. Lacasse, F.X., Hildgen, P., Pérodin, J., Escher, E., Phillips, N.C., McMullen, J.N. Pharm. Res. (1997) [Pubmed]
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