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Open AccessArticle

Preparation and Evaluation of Resveratrol-Loaded Composite Nanoparticles Using a Supercritical Fluid Technology for Enhanced Oral and Skin Delivery

College of Pharmacy, Pusan National University, 63 Busandaehak-ro, Geumjeong-gu, Busan 46241, Korea
Dong-A ST Co. Ltd., Giheung-gu, Yongin, Gyeonggi 446-905, Korea
College of Pharmacy, Kyungsung University, 309, Suyeong-ro, Nam-gu, Busan 48434, Korea
Department of Pharmaceutical Engineering, Inje University, Gyeongnam 621-749, Korea
Department of Industrial and Physical Pharmacy, College of Pharmacy, Purdue University, 575 Stadium Mall Drive, West Lafayette, IN 47907, USA
College of Pharmacy and Yonsei Institute of Pharmaceutical Sciences, Yonsei University, 85 Songdogwahak-ro, Yeonsu-gu, Incheon 21983, Korea
Author to whom correspondence should be addressed.
Antioxidants 2019, 8(11), 554;
Received: 2 November 2019 / Revised: 12 November 2019 / Accepted: 13 November 2019 / Published: 14 November 2019
(This article belongs to the Special Issue Natural Phenolic Compounds for Health, Food and Cosmetic Applications)
We created composite nanoparticles containing hydrophilic additives using a supercritical antisolvent (SAS) process to increase the solubility and dissolution properties of trans-resveratrol for application in oral and skin delivery. Physicochemical properties of trans-resveratrol-loaded composite nanoparticles were characterized. In addition, an in vitro dissolution–permeation study, an in vivo pharmacokinetic study in rats, and an ex vivo skin permeation study in rats were performed. The mean particle size of all the composite nanoparticles produced was less than 300 nm. Compared to micronized trans-resveratrol, the trans-resveratrol/hydroxylpropylmethyl cellulose (HPMC)/poloxamer 407 (1:4:1) nanoparticles with the highest flux (0.792 μg/min/cm2) exhibited rapid absorption and showed significantly higher exposure 4 h after oral administration. Good correlations were observed between in vitro flux and in vivo pharmacokinetic data. The increased solubility and flux of trans-resveratrol generated by the HPMC/surfactant nanoparticles increased the driving force on the gastrointestinal epithelial membrane and rat skin, resulting in enhanced oral and skin delivery of trans-resveratrol. HPMC/surfactant nanoparticles produced by an SAS process are, thus, a promising formulation method for trans-resveratrol for healthcare products (owing to their enhanced absorption via oral administration) and for skin application with cosmetic products. View Full-Text
Keywords: resveratrol; solubility; nanoparticle; correlation; supercritical fluid; bioavailability resveratrol; solubility; nanoparticle; correlation; supercritical fluid; bioavailability
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MDPI and ACS Style

Ha, E.-S.; Sim, W.-Y.; Lee, S.-K.; Jeong, J.-S.; Kim, J.-S.; Baek, I.-H.; Choi, D.H.; Park, H.; Hwang, S.-J.; Kim, M.-S. Preparation and Evaluation of Resveratrol-Loaded Composite Nanoparticles Using a Supercritical Fluid Technology for Enhanced Oral and Skin Delivery. Antioxidants 2019, 8, 554.

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