METHODS OF MAKING NANOCRYSTALS WITH ENHANCED BIOLOGICAL AVAILABILITY AND FORMULATION FOR SUCH NANOCRYSTALS PREPARATION FOR USE IN ANTICANCER THERAPY

摘要

The method of nanocrystal preparation is based on the procedure of the crystalline nanoparticles preparation in powder form that comprises a) dissolving the protonated nitrogen containing derivatives of camptothecin and curcuminoids in an organic solvent leading to formation of self-assembled ionic complex followed by subsequent addition of nonionogenic injectable surfactant, b) transferring the obtained mixture into aqueous medium under continuous homogenization including mixing, shaking and/or using ultrasound, c) removing the solvent in order to obtain powder form, d) lyophilisation of the product with the previously added cryoprotectant. Composition for nanocrystal preparation through the method according to the invention consists of injectable nonionic surfactant and self-assembled ionic complex that contains curcuminoids and protonated nitrogen containing derivatives of camptothecin and its analogues in the molar ratios in the range between 10:1 and 1:10. Analogues of camptothecin include preferably camptothecin and homocamptothecin. Protonated nitrogen containing camptothecin derivatives preferably have the protonated nitrogen included in their chemical structure through at least one functional group including primary amine, secondary amine, tertiary amine, cyclic amine and/or their combinations. Utilization of nanocrystals prepared for the anticancer injectable drug application consists in the dissolution of 3 wt. % nanocrystals in powder form in the liquid medium based on distilled water with 5 wt. % of glucose.