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

Microparticles were produced by spray-drying from a high molecular weight polylactide (PLA R207) for the development of long-lasting controlled release systems of vaccines, which may be designed to obviate the need for booster doses. The current investigation considered the effect of both technological parameters (inlet air temperature and spray rate of feed) and polymeric solutions (polymer concentration and nature of organic solvents) on characteristics of microparticles (morphology, size and antigen loading) containing a water-soluble model antigen (bovine serum albumin, BSA). Following parameters 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 18.20 +/- 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 temperature, the spray-rate of feed or the use of a mixture of dichloromethane/chloroform (DCM/CFM) instead of DCM alone resulted in the modification of the 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 while the burst release was not modified, SDS-PAGE electrophoresis and isoelectric focusing analyses of the BSA released from microparticles confirmed the preservation of its physicochemical characteristics. Together, results showed that the spray-dried microparticles loaded with hydrophilic antigen could be used as a potential delivery system for the long-lasting controlled release of vaccines. (C) 2000 Elsevier Science B.V. All rights reserved.