Incorporation of 10-hydroxycamptothecin nanocrystals into zein microspheres

Abstract

Incorporation of drug nanocrystal (DNC) into a particulate carrier to form the DNC delivery system was conducted in this study, where 10-hydroxycamptothecin (HCPT) was selected as the model drug and zein was the carrier. The supercritical anti-solvent (SAS) process or the built-in ultrasonic dialysis process (BUDP) was applied to prepare HCPT NC-loaded zein microspheres (HCPT NC-Zein MS) at first respectively, but the results showed that the products obtained were unsatisfactory in their particle microstructures. Fortunately, by combining the SAS process with BUDP, i.e. the co-precipitation of HCPT and zein prepared using the SAS process was dispersed into ethanol–water as the dialysis solution for BUDP, the results showed that desirable HCPT NC-Zein MS were obtained. The formulations were evaluated quantitatively by an overall desirability function (DF), and the optimized HCPT NC- Zein MS was prepared according to the range analysis results of DF. Under the optimized conditions, HCPT NC-Zein MS with a mean particle size=1.10±0.12µm, drug loading=5.98% and encapsulation efficiency=95.68% were obtained. The further characterizations of SEM, FT-IR, XRD and DSC demonstrated that HCPT NC was successfully incorporated into the interior of zein microspheres. The effects of the process parameters and the formation mechanism of HCPT NC-Zein MS were discussed in detail. Furthermore, it is presented that HCPT NC-Zein MS sustained HCPT release rate successfully, where about 50% HCPT was fast released in the first 20h, then the release trend followed zero order kinetics and reached 70% in 82h.