Design and self-assembly of nanomicelles loading 5-fluorouracil-ferulic acid cocrystal with synergistic antitumor activity: toward efficient encapsulation and sustained-release effect.

OBJECTIVE

The research is aimed at fulfilling long-term and high-performance synergistic anticancer effects of 5-fluorouracil (Flu), opening up new horizons for drug-nutrient cocrystal formulation.

METHODS

An integration strategy of cocrystallization and micellar preparation techniques is established. The former targets to play synergistic effects by introducing nutriment ferulic acid (FR), and meanwhile, enhances the interplay with polymers to promote efficient encapsulation, whereas the latter focuses on the modulation of release behavior. Based on this clue, cocrystal Flu-FR-H2O with synergistic ability is loaded in carriers to prepare cocrystal nanomicelles. The cocrystal nanomicelles were characterized by dynamic light scattering (DLS) and transmission electron microscope (TEM), with the in vivo/vitro biopharmaceutical properties evaluated.

RESULTS

The obtained nanomicelles exhibit preferable encapsulation efficiency, as supported by theoretical simulation calculations. This higher efficient entrapment has positive impacts on antitumor efficacy and pharmacokinetic behavior. Particularly, the cocrystal micelles can provide sustained-release ability, thus facilitating the lasting-efficacy.

CONCLUSION

This investigation exemplifies the availability of the integrated strategy in realizing transformation of Flu-nutraceutical cocrystal dosage form, therefore contributing to the technical support for synergistic antitumor pharmaceutical cocrystal formulations.