Preparation and characterization of pH-sensitive camptothecin-cis-aconityl grafted chitosan oligosaccharide nanomicelles

Camptothecin (CPT) was introduced to water-soluble chitosan oligosaccharide (CHO) using cis-aconityl (CA), as a pH-sensitive linker, to develop a new hydrophobic structure, i.e. CPT-CA-CHO. The triple conjugates were synthesized in three ratios (5%, 7.5%, and 10%) and characterized by Fourier transform infrared (FT-IR) and proton nuclear magnetic resonance ((HNMR)-H-1). Thermo gravimetric analysis and critical micelle concentration (CMC) assessments were performed. Prepared nano-micelles were analyzed for particle size, polydispersity index (PDI), drug release and in vitro cytotoxicity. CPT-CA-CHO 7.5% micelles as optimum micelles had a mean diameter of 50 nm (observed by transmission electron microscopy), a zeta potential of +45.9 mV, and a CMC of about 9.97 x 10(-5) g/L. The release results showed that CPT-CA-CHO 7.5% has the burst release at acidic pH, and cytotoxicity study indicated that IC50 of CPT-CA-CHO 7.5% for MCF-7 cell line was 0.8 mu g/mL. These properties altogether make CPT-CA-CHO micelles, as a pH sensitive cargo with inherent cytotoxicity, a potential candidate for hydrophobic anticancer drugs. (C) 2016 Published by Elsevier B.V.