Promoted Transfection Efficiency of pDNA Polyplexes-Loaded Biodegradable Microparticles Containing Acid-Labile Segments and Galactose Grafts

Targeting to antigen-presenting cells and efficient intracellular delivery of pDNA are essential for development of microsphere formulations of DNA vaccine. Biodegradable polymers containing acid-labile segments and galactose grafts were developed to entrap pDNA polyplexes into microspheres, which were proposed to promote transfection efficiency of pDNA. Acid-labile characteristics were approved by the hemolysis capabilities of red blood cells and degradation behaviors of matrix polymers; release of pDNA polyplexes from microspheres was significantly accelerated after incubation in acid buffers. Presence of galactose moieties enhanced cellular uptake of microspheres and increased acid-lability due to hydrophilic grafts on acid-labile segments. There was no apparent cytotoxicity of blank microspheres; cytotoxicity of pDNA polyplexes was significantly decreased after encapsulation into and sustained release from microspheres. High transfection efficiency and a dose-dependent transfection were indicated for pDNA polyplex-loaded acid-labile microspheres when balancing with cytotoxicity. Integration of acid-lability, targeting effect into full biodegradable backbone represents an exciting approach to promote transfection efficiency through modulating release of pDNA polyplexes, targeting to antigen-presenting cells and intracellular delivery of pDNA.