Zhu Chen1, Xiaojun Cai, Ye Yang, Guannan Wu, Yaowen Liu, Fang Chen, Xiaohong Li. 1. Key Laboratory of Advanced Technologies of Materials Ministry of Education of China, School of Materials Science & Engineering, Southwest Jiaotong University, Chengdu, 610031, People's Republic of China.
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.
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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