Purpose the purpose of this work was to enhance the dissolution of insoluble drug by developing an innovative water-free method of preparing multiunit cubosome precursor microparticles (CPMs), which would spontaneously self-assemble to homogenous cusomes.Methods CPMs containing insoluble model drug docetaxel (DTX) were prepared from GMO and PVP K30 in different weigh ratio by simple one-step process of spray drying, and spontaneously self-assemble to homogeneous in situ cubosome dispersion upon being exposed to aqueous medium during administration.The testing methods including laser particle size analyzer (LPS), differential scanning calorimetry (DSC) and scanning electron microscope (SEM) were employed to characterize CPMs morphology and physiochemical properties.The phase behavior and internal structure of were assessed by crossed polarized light microscope (CPLM) and small angle X-ray scattering (SAXS).Results and discussion These formulations of self-assembly cubosomes possessed significantly higher drug entrapment efficiency (EE) from 91.7%~96.3% than that of cubosomes prepared by other conventional methods.The CPMs were spherical particles with size diameter in the range of 10~20 μm while the size diameter of self-assembly cubosomes were 150~200 um.The size shift may be attributing to PVP dissolution and the multiunit CPMs disintegration into a great number of nanosized cobosomes.In DSC assay,DTX characteristic peak of DTX loaded CPMs disappeared, indicating that dispersed DTX was in the amorphous form which would facilitate drug dissolution.Under cross-polarizer,the cubosomes displayed isotropic property, indicative of cubic phase, and then the specific crystal structure was validated to be Im3m space with scattering peak position ratios of.The inner nanostructured bicontinuous water channels were reported to play a pivotal role in improving drug dissolution and diffusion rate.In vitro study, the cumulative drug release of DTX loaded CPMs was up to 93.4% while76.2% for the physical mixture of blank CPMs within 120 min, manifesting that the CPMs significantly enhanced the dissolution of poorly water soluble drug and hence be able to improve the bioavailability.Conclusion a feasible and efficient water-free technique was used to obtain homogeneous cubosomes with separating two congruent networks of water channels by self-assembling of CPMs.The amphiphilic property and unique inner nanostructure of the self-assembly cubosome made it an excellent carrier for insoluble drugs.As precursor microparticles, the CPMs showed the powder characteristics which would be convenient for storage and usage.Furthermore, these precursor powders could be developed into tablet, capsule and other dosage forms with extensive applications for various routes of administration.An accelerated progress of cubosome industrial manufacture was achieved as the cubosome carrier was designed as water-free multiunit precursor microparticles.