Central composite design optimizes preparation of norcantharidin-loaded chitosan-fibroin microspheres for embolization

Objective: To develop a preparation technique,and to determine the envelop efficiency,drug loading and the surface morphology of the norcantharidin-loaded chitosan-fibroin microspheres(NCTD-CS-SF-MS),and the release dynamics of NCTD-CS-SF-MS in vitro by dynamic dialysis system.Methods: NCTD-CS-SF-MS were achieved by emulsification cross-linking process with liquid paraffin as oil phase.The hybrid of chitosan(CS) and silk fibroin(SF) was used as water phase,Span-80 as emulsifier,and glutaraldehyde as cross linking agent.The central composite design was applied to optimize the formulation and preparation procedure.The surface morphology of the microspheres was observed by scanning electron microscopy(SEM),the interaction of the drug and the polymer was analyzed by XRD and DSC.Dynamic dialysis method was used to determine the release characteristic of norcantharidin from microspheres in vitro.Results: The microspheres with a global shape and narrow size distribution were prepared.Its average diameter was(184±5) μm,the drug loading and the envelop efficiency of microspheres were(15.08±2.85)% and(27.46±1.25)%,respectively.All the drug release behaviors at 0.1 mol·L-1 HCl,phosphate buffered saline(pH=7.4) and saline followed Weibull distribution model.Conclusion: The optimized preparation technique is feasible,by which NCTD-CS-SF-MS with evident effect of sustained drug release are prepared.