Parameters influencing the antigen release from spray-dried poly(DL-lactide) microparticles

Microparticles were produced by spray-drying from a high molecular weight p olylactide (PLA R207) for the development of long-lasting controlled releas e systems of vaccines, which may be designed to obviate the need for booste r doses. The current investigation considered the effect of both technologi cal parameters (inlet air temperature and spray rate of feed) and polymeric solutions (polymer concentration and nature of organic solvents) on charac teristics of microparticles (morphology, size and antigen loading) containi ng a water-soluble model antigen (bovine serum albumin, BSA). Following par ameters chosen, microparticles were characterized by a mean size from 3.08 +/- 0.06 to 9.43 +/- 0.26 mu m and a BSA loading from 2.45 +/- 0.13 to 18.2 0 +/- 2.25% (w/w). The BSA release rate from microparticles varied from 11. 17 +/- 2.20 to 92.60 +/- 3.46% in 24 h. The modification of the inlet tempe rature, the spray-rate of feed or the use of a mixture of dichloromethane/c hloroform (DCM/CFM) instead of DCM alone resulted in the modification of th e BSA burst release. This burst release was followed by a BSA release rate slower for microparticles with a low BSA loading. Moreover, the increase of the R207 concentration resulted in a decrease of the BSA release rate whil e the burst release was not modified, SDS-PAGE electrophoresis and isoelect ric focusing analyses of the BSA released from microparticles confirmed the preservation of its physicochemical characteristics. Together, results sho wed that the spray-dried microparticles loaded with hydrophilic antigen cou ld be used as a potential delivery system for the long-lasting controlled r elease of vaccines. (C) 2000 Elsevier Science B.V. All rights reserved.