A novel composite hydrogel based on chitosan and inorganic phosphate for local drug delivery of camptothecin nanocolloids

Abstract

In attempt to overcome the problem of low water solubility and severe toxicity of camptothecin (CPT) after intravenous administration, a novel drug carrier system based on chitosan (CS) and dibasic sodium phosphate (DSP) has been developed in this paper to encapsulate CPT intending for local administration. Nanocolloids of CPT with size about 500nm were first prepared, followed by encapsulation in the chitosan/dibasic sodium phosphate (CS/DSP) formulation. The formulation was sol state below 37°C and transformed to nonflowing gel state at 37°C. Encapsulation of CPT nanocolloids had greatly effect on the gelling time as well as the micro-structure of hydrogel. In vitro and in vivo degradation studies revealed that the developed CS/DSP hydrogel was biodegradable and biocompatible. In vitro release study revealed that CPT released from CS/DSP hydrogel in an extended period with about 70% of total CPT released from hydrogel after 18 days. Furthermore, nearly 90% of CPT in the chitosan hydrogels could be preserved in the lactone form (active form) even after 7 days's storage at 37°C. Furthermore, in vitro cytotoxicity of CPT nanocolloids on SKOV3 human ovarian cancer cells suggested the well anti-tumor cell efficiency could be gained at a lower concentration. © 2010 Wiley-Liss, Inc.