pH-sensitive chitosan-derived nanoparticles as doxorubicin carriers for effective anti-tumor activity: preparation and in vitro evaluation

• Published in: Colloids and surfaces, B, Biointerfaces Vol. 94; pp. 184 - 191
• Main Authors: Jin, Yun-Huan, Hu, Hai-Yang, Qiao, Ming-Xi, Zhu, Jia, Qi, Jia-Wei, Hu, Chan-Juan, Zhang, Qiang, Chen, Da-Wei
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.06.2012
• Subjects: Antibiotics, Antineoplastic - administration & dosage; Antibiotics, Antineoplastic - pharmacology; Antitumor activity; Cell Line, Tumor; Chitosan - analogs & derivatives; Chitosan - chemistry; Chitosan derivatives; Delayed-Action Preparations; Deoxycholic Acid - chemistry; Dose-Response Relationship, Drug; Doxorubicin; Doxorubicin - administration & dosage; Doxorubicin - pharmacology; Drug Carriers; Drug resistance; Drug Resistance, Neoplasm - drug effects; Female; Flow Cytometry; Humans; Hydrogen-Ion Concentration; Microscopy, Confocal; Nanoparticles; Particle Size; pH-sensitive; Nanoparticles; pH-sensitive; Antitumor activity; Chitosan derivatives; Drug resistance; Doxorubicin
• ISSN: 0927-7765; 1873-4367
• DOI: 10.1016/j.colsurfb.2012.01.032

[Display omitted] ► We have developed a chitosan-derived nanocarrier system for hydrophobic anticancer drugs. ► This system exhibited an acidic pH-induced aggregation, deformation and accelerated drug release profile. ► This system was also much more effective than the free drug against drug-resistant cancer cells. pH-sensitive self-aggregated nanoparticles (SNPs), based on amphiphilic deoxycholic acid (DOCA) modified carboxymethyl chitosan (DCMC), were prepared for delivery of the anticancer drug doxorubicin (DOX). DCMCs with different degrees of substitution (DS) of DOCA were initially synthesized and characterized. Based on self-aggregation, DCMC formed nanoparticles with size ranging from 87 to 174nm. The critical aggregation concentration (CAC) decreased on increasing the DS of DOCA. Moreover, the DCMC SNPs showed an acidic pH-induced aggregation and deformation behavior. The DOX-loaded SNPs ([D]NP) exhibited a sustained drug release manner, which could be accelerated by an acidic pH, but delayed by a higher DS of DOCA. Antitumor efficacy results showed that [D]NP could suppress both sensitive and resistant MCF-7 cells effectively in a dose- and time-dependent manner. The enhanced cellular uptake and greater retention of [D]NP in drug-resistant cells, as evidenced by confocal microscopy and flow cytometry, contributed to a superior efficacy of [D]NP over free DOX. These results suggest the potential of DCMC SNPs as carriers for the hydrophobic drug DOX for effective cancer therapy against drug-resistant tumors.