Tumour targeted delivery of encapsulated dextran-doxorubicin conjugate using chitosan nanoparticles as carrier

Doxorubicin (DXR) commonly used in cancer therapy produces undesirable side effects such as cardiotoxicity. To minimize these, attempts have been made to couple the drug with dextran (DEX) and then to encapsulate this drug conjugate in hydrogel nanoparticles. By encapsulation of the drug conjugate in biodegradable, biocompatible long circulating hydrogel nanoparticles, we further improved the therapeutic efficacy of the conjugate. The size of these nanoparticles as determined by quasi-elastic light scattering, was found to be 100 +/- 10 nm diameter, which favors the enhanced permeability and retention effect (EPR) as observed in most solid tumors. The antitumor effect of these DEX-DXR nanoparticles, was evaluated in J774A.1 macrophage tumor cells implanted in Balb/c mice. The in vivo efficacy of these nanoparticles as antitumor drug carriers, was determined by tumor regression and increased survival time as compared to drug conjugate and free drug. These results suggest that encapsulation of the conjugate in nanoparticles not only reduces the side effects, but also improves its therapeutic efficacy in the treatment of solid tumors. (C) 2001 Elsevier Science B.V. All rights reserved.