**4. Conclusions**

In our study, we designed HPMC/surfactants nanoparticles using the supercritical antisolvent (SAS) process in order to increase solubility and dissolution properties of *trans*-resveratrol for effective oral and skin delivery. Spherical composite nanoparticles with a mean size smaller than 300 nm were successfully produced using an SAS process. Among the formulations tested, *trans*-resveratrol/HPMC/poloxamer 407 (1:4:1) nanoparticles show the highest flux of 0.792 μg/min/cm<sup>−</sup>2, exhibit rapid absorption, and have significantly higher exposure 4 h after oral administration than micronized *trans*-resveratrol. Good correlations between in vitro flux and in vivo pharmacokinetic data were also observed. The increased solubility and flux of *trans*-resveratrol generated using HPMC/surfactant nanoparticles increased driving forces on the gastrointestinal epithelial membrane and rat skin, resulting in enhanced oral and skin delivery of *trans*-resveratrol. HPMC/surfactant nanoparticles produced by the SAS process are, therefore, promising formulations enhancing *trans*-resveratrol absorption via oral administration for use in healthcare products, as well for skin application of cosmetic products.

**Author Contributions:** Conceptualization, E.-S.H., J.-S.K., S.-J.H., and M.-S.K.; formal analysis, E.-S.H., W.-Y.S., S.-K.L., J.-S.J., J.-S.K., I.-h.B., D.H.C., H.P., and M.-S.K.; funding acquisition, M.-S.K.; investigation, E.-S.H., W.-Y.S., S.-K.L., and M.-S.K.; methodology, E.-S.H., W.-Y.S., S.-K.L., J.-S.J., J.-S.K., I.-h.B., D.H.C., H.P., and M.-S.K.; software, D.H.C., S.-J.H., and M.-S.K.; supervision, M.-S.K.; validation, E.-S.H.; writing—original draft, E.-S.H. and M.-S.K.; writing—review and editing, J.-S.K., I.-h.B., D.H.C., H.P., S.-J.H., and M.-S.K.

**Funding:** This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF), funded by the Ministry of Science, ICT, and Future Planning (NRF- 2017R1C1B1006483).

**Conflicts of Interest:** The authors declare no conflict of interest.
