Department of Pharmaceutical Technology, Centre for Excellence in Nanobio Translational Research (CENTRE), Anna University, BIT Campus, Tiruchirappalli 620024, Tamil Nadu, India.
Department of Pharmaceutical Technology, Centre for Excellence in Nanobio Translational Research (CENTRE), Anna University, BIT Campus, Tiruchirappalli 620024, Tamil Nadu, India; National Facility for Drug Development for Academia, Pharmaceutical and Allied Industries (NFDD), Anna University, BIT Campus, Tiruchirappalli 620024, Tamil Nadu, India.
Carbohydr Polym. 2017 Feb 10;157:1677-1686. doi: 10.1016/j.carbpol.2016.11.049. Epub 2016 Nov 18.
A chitosan-hydrazone-mPEG (CH-Hz-mPEG) copolymer which is stable at extracellular pH and cleaves at slightly acidic intracellular pH was synthesized and characterized. Blank polymeric nanoparticles (B-PNPs) and prednisone-loaded polymeric nanoparticles (P-PNPs) were then formulated by dialysis/precipitation method. The cell-specific ligand, atrial natriuretic peptide (ANP) was then conjugated to P-PNPs (ANP-P-PNPs) by a coupling reaction. Particle size and morphological analyses revealed uniform spherical shape of PNPs. In vitro pH dependent degradation of PNPs was investigated. Drug release profile of ANP-P-PNPs indicated a slow release of prednisone at pH 7.4, but a rapid release at pH 5.0 due to the cleavage of hydrazone linkage. Cytotoxicity studies demonstrated greater compatibility of B-PNPs compared to ANP-P-PNPs. Cellular internalization of ANP-P-PNPs was higher than P-PNPs owing to receptor-mediated endocytosis. The results from this investigation support the hypothesis that chitosan based ANP-P-PNPs could act as an intracellular pH-responsive and targeted drug delivery system.
合成并表征了一种壳聚糖腙-甲氧基聚乙二醇（CH-Hz-mPEG）共聚物，该共聚物在细胞外 pH 值下稳定，而在稍酸性的细胞内 pH 值下分解。然后通过透析/沉淀法制备空白聚合物纳米粒（B-PNPs）和负载泼尼松的聚合物纳米粒（P-PNPs）。然后通过偶联反应将细胞特异性配体心钠肽（ANP）连接到 P-PNPs（ANP-P-PNPs）上。颗粒大小和形态分析显示 PNPs 呈均匀的球形。研究了 PNPs 在 pH 值依赖性体外降解。ANP-P-PNPs 的药物释放曲线表明，由于腙键的断裂，泼尼松在 pH 值为 7.4 时缓慢释放，但在 pH 值为 5.0 时快速释放。细胞毒性研究表明，与 ANP-P-PNPs 相比，B-PNPs 具有更好的相容性。由于受体介导的内吞作用，ANP-P-PNPs 的细胞内化率高于 P-PNPs。该研究结果支持了壳聚糖基 ANP-P-PNPs 可作为细胞内 pH 响应和靶向药物传递系统的假设。
