Atrial natriuretic peptide-conjugated chitosan-hydrazone-mPEG copolymer nanoparticles as pH-responsive carriers for intracellular delivery of prednisone

作者：Antoniraj M Gover; Kumar C Senthil; Kumari Henry Linda Jeeva; Natesan Subramanian; Kandasamy Ruckmani^*

来源：Carbohydrate Polymers, 2017, 157: 1677-1686.

DOI：10.1016/j.carbpol.2016.11.049

• Chitosan
• Conjugated polymers
• Atrial natriuretic peptide (ANP)
• Stimuli-sensitive polymers
• Copolymer nanoparticles
• Targeted drug delivery

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.

• 出版日期2017-2-10
• 单位北京理工大学