Preparation of carboxymethylchitosan nanoparticles with Acid-sensitive bond based on solid dispersion of 10-hydroxycamptothecin.

Abstract

Solid dispersions were prepared by a conventional solvent evaporation method from the water-insoluble model drug 10-hydroxycamptothecin (HCPT) and monomethoxypoly(ethylene glycol) 2000 (mPEG 2000). And then one type of novel biodegradable nanoparticles, the solid dispersion (HCPT/mPEG-CHO) grafted with carboxymethylchitosan (HCPT/mPEG-g-CMCTS) was synthesized. The increase in HCPT solubility of solid dispersion was up to 21-fold compared with the original drug. With the increasing of the amount of mPEG-CHO, solubility of HCPT was from 7.71 μg/mL to 25.82 μg/mL. Colloid systems based on solid dispersion were stable in aqueous medium at 5°C. After 5 months storage at 25°C, the solid dispersions do not change at all. HCPT/mPEG-g-CMCTS was synthesized by grafting reaction of carboxymethylchitosan with mPEG-CHO to form Schiff base which is sensitive to acid environment. The release rate of HCPT from this conjugate in pH 5.4 was much higher than that in the environment of pH 7.4 and p H 4.5. The cumulative release percentages are 45%, 25%, and 15%, respectively. The cumulative release percentage of HCPT in conjugate was only 15% within 85 h while the original drug was up to 70% in pH 7.4, showing a significant slow-release property. This drug model can be attractive candidates as delivery biosystems in tumor therapy.