Novel super pH-sensitive nanoparticles responsive to tumor extracellular pH

The objective of this study was to evaluate Camptothecin (CAMP)-loaded poly(N-isopropylacrylamide) (NIPAAm)/chitosan nanoparticles as a pH-sensitive carrier for specifically targeting tumors. The synthesis and properties of the system was studied by adjusting the mass ratio of NIPAAm and chitosan. The drug release characteristics of nanoparticles in vitro were investigated. The results showed that when the charge ratio between NIPAAm and chitosan of 4:1 (w/w) was achieved, the drug-loaded nanoparticles were most sensitive to tumor pH. Encapsulation efficiencies and loading were 73.7% and 8.4%, respectively. The cumulative release rate of CAMP was optimal at pH 6.8 and decreased rapidly either below pH 6.5 or above pH 6.9 in 37 degrees C. Based on MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium) test and fluorescence microscopy results, CAMP-loaded nanoparticles showed cytotoxicity at pH 6.8 but minimal cytotoxicity at pH 7.4. The pH-sensitive poly NIPAAm/chitosan nanoparticles provided some distinct advantages in delivering anti-cancer drugs to targeted tissues. (C) 2007 Elsevier Ltd. All rights reserved.