ABSTRACT
Purpose
Targeting to antigen-presenting cells and efficient intracellular delivery of pDNA are essential for development of microsphere formulations of DNA vaccine.
Methods
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.
Results
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.
Conclusions
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.
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ACKNOWLEDGMENTS & DISCLOSURES
This work was supported by National Natural Science Foundation of China (30570501, 20774075, and 51073130), and Fundamental Research Funds for the Central Universities (SWJTU09ZT21).
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The particular synthesis and characterization results of PGBELA were included in the supplementary materials.
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Chen, Z., Cai, X., Yang, Y. et al. Promoted Transfection Efficiency of pDNA Polyplexes-Loaded Biodegradable Microparticles Containing Acid-Labile Segments and Galactose Grafts. Pharm Res 29, 471–482 (2012). https://doi.org/10.1007/s11095-011-0577-4
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DOI: https://doi.org/10.1007/s11095-011-0577-4