Preparation and evaluation of physicochemical properties of etoposide nano-mixed micelles

Abstract

In order to enhance the aqueous solubility and stability of etoposide preparation,the central composite design-response surface method was used to optimize the prescription technology of etoposide nano-mixed micelles (ETP mPEG-PLA/P123).Based on the results of single factor test,central composite design-response surface method of three factors and five levels was carried out to optimize the prescription technology with drug dosage,the mass ratio of mPEG-PLA and hydration volume as independent variables,and the entrapment efficiency,drug loading and particle size as dependent variables.The critical micelle concentration (CMC) was determined by fluorescence probe method,and the physicochemical properties and release behavior of the prepared micelle preparations were evaluated.The results showed that the optimal prescription of ETP mPEG-PLA/P123 micelle preparation was that mPEG-PLA∶P123=38∶62,the drug dosage was 5 mg,and the hydration volume was 6 mL.After optimization,the entrapment efficiency and drug loading were 874% and 419%,the particle size was 1156 nm,PDI was 0216,and Zeta potential was -163 mV.The CMC value was 17×10-3 </sup>g/L,so mPEG-PLA/P123 micelles had high stability.In vitro release experiments,etoposide could be released from micelles slowly and continuously,up to 80% within 48 h.The optimized ETP mPEG-PLA/P123 nano-mixed micelles were able to enormously improve the aqueous solubility of etoposide,and the micelle preparation had good stability and a certain slow-release effect.The results of this study could provide theoretical guidance for further broadening the range of application of new etoposide preparations.

Keywords

• pharmaceutics; etoposide; p123; micelles; uplc; thin film hydration method; central composite design-response surface method