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.
Pharm Res. 2012 Feb;29(2):471-82. doi: 10.1007/s11095-011-0577-4. Epub 2011 Sep 1.
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.
针对抗原呈递细胞和有效细胞内递送 pDNA 是 DNA 疫苗微球制剂发展的关键。
开发了含有酸不稳定段和半乳糖接枝的可生物降解聚合物，将 pDNA 多聚物包埋到微球中，以提高 pDNA 的转染效率。
红血细胞的溶血能力和基质聚合物的降解行为证明了酸不稳定的特点；在酸性缓冲液中孵育后，pDNA 多聚物从微球中的释放明显加速。半乳糖部分的存在增强了微球的细胞摄取能力，并由于亲水接枝在酸不稳定段上而增加了酸不稳定。空白微球没有明显的细胞毒性；pDNA 多聚物的细胞毒性在包封到微球中和从微球中持续释放后显著降低。当平衡细胞毒性时，负载 pDNA 多聚物的酸不稳定微球具有高转染效率和剂量依赖性转染。
将酸不稳定、靶向作用整合到全可生物降解的骨架中，是一种通过调节 pDNA 多聚物的释放、靶向抗原呈递细胞和 pDNA 的细胞内递送来提高转染效率的激动人心的方法。
