Enhanced oral bioavailability of self-assembling curcumin–vitamin E prodrug-nanoparticles by co-nanoprecipitation with vitamin E TPGS

Abstract

Curcumin (CUR), a nontoxic natural compound with potent antitumor activity, was limited in clinical application due to its insolubility and exceedingly low bioavailability. In this study, a novel prodrug-nanoparticle (CSSV/TPGS-NPs) self-assembled by co-nanoprecipitation of CUR-s-s-vitamin E conjugate and d-alpha-tocopheryl polyethylene glycol 1000 succinate (vitamin E TPGS) was prepared in attempt to solve aforementioned obstacles. CSSV/TPGS-NPs showed smaller sizes and better stability compared with that of CUR-s-s-vitamin E conjugate prodrug-nanoparticles (CSSV-NPs). Significantly, the absorption constant and effective permeability of CSSV/TPGS-NPs in different intestinal tracts increased 1.31–2.78 times and 1.81–6.95 times than that of CUR suspension, respectively. Pharmacokinetic study in Sprague-Dawley (SD) rats demonstrated that orally administered CSSV/TPGS-NPs displayed a prolonged plasma circulation with 8.06-fold increase in relative bioavailability compared to that of the CUR suspension. Altogether, conjugation of hydrophobic native CUR with vitamin E to form CSSV/TPGS-NPs is a promising technology for sustained and controlled drug delivery of CUR with improved oral bioavailability in vivo.

Keywords:

• Curcumin
• prodrug-nanoparticles
• oral bioavailability
• TPGS
• controlled release

Disclosure statement

The authors declare that they have no conflicts of interest.

Additional information

Funding

This work was supported by China Postdoctoral Science Foundation (2018M630533), Program for Scientific Research Innovation Team in Colleges and Universities of Jiangsu Province and a project funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions. This work was also supported by the National Natural Science Foundation of China (Grant No. 81803475).