Preparation and characterization of poly-DL-lactide-poly(ethylene glycol) microspheres containing λDNA

Polylacticle (PLA) and a block copolymer, poly-DL-lactide-poly(ethylene glycol) (PELA) were synthesized by bulk ring-opening polymerization initiated by stannous chloride. A linear DNA molecule, lambdaDNA, was used as the model DNA. PLA, PELA, lambdaDNA-loaded PLA and PELA microspheres were prepared by the solvent-extraction method based on the formation of multiple w(1)/o/w(2) emulsion. The particle-size distribution, surface morphology, and DNA loading characterized the microspheres. The mean diameter of lambdaDNA-loaded PELA microspheres was proved to be 3.5 mum. The integrity of the lambdaDNA molecules, after preparing the microspheres, was determined by agarose gel electrophoresis. The result suggested that most of the lambdaDNA molecules could retain their integrity after being encapsulated by PELA. The PELA microspheres could also prevent lambdaDNA from being degraded by DNase. The in vitro degradation and release of PLA, PELA, and lambdaDNA-loaded PELA microspheres were carried out in a pH 7.4 buffer solution at 37degreesC. Quantitatively, evaluating the molecular weight reduction, the mass loss, the particle-size changes, and the particle-size distribution changes also monitored the degree of degradation. The release profile was assessed by measurement of the amount of lambdaDNA present in the release medium at determined intervals. The degradation profiles of the PELA microspheres were quite different from those of the PLA microspheres. The introduction of the hydrophilic poly(ethylene glycol) domain in PLA and the presence of lambdaDNA within the microspheres exhibit the apparent influence on the degradation and release profiles. A biphasic release profile was proved, that is, an initial burst release during the first days, then a gradual release. It was demonstrated that the PELA microspheres could be used potentially as a controlled release-delivery system for lambdaDNA. (C) 2002 Wiley Periodicals, Inc.