Pomegranate Seed Oil Exerts Synergistic Effects with trans-Resveratrol in a Self-nanoemulsifying Drug Delivery System

• Published in: Biological & pharmaceutical bulletin Vol. 38; no. 10; pp. 1658 - 1662
• Main Authors: Lu, Lu-yang, Liu, Yuan, Zhang, Zhi-feng, Gou, Xiao-jun, Jiang, Jun-hao, Zhang, Ji-zhong, Yao, Qian
• Format: Journal Article
• Language: English
• Published: Japan The Pharmaceutical Society of Japan 01.10.2015; Japan Science and Technology Agency
• Subjects: Animals; anti-inflammation; Anti-Inflammatory Agents - administration & dosage; Anti-Inflammatory Agents - pharmacology; Anti-Inflammatory Agents - therapeutic use; anticancer activity; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; Carrageenan; Cell Survival - drug effects; Drug Delivery Systems; Drug Synergism; Edema - chemically induced; Edema - drug therapy; Gastric Juice - chemistry; Humans; Intestinal Secretions - chemistry; MCF-7 Cells; Mice; Plant Oils - administration & dosage; Plant Oils - chemistry; Plant Oils - pharmacology; Plant Oils - therapeutic use; pomegranate seed oil; Punicaceae; Seeds; self-nanoemulsification; Solubility; Stilbenes - administration & dosage; Stilbenes - pharmacology; Stilbenes - therapeutic use; trans-resveratrol; Water - chemistry
• ISSN: 0918-6158; 1347-5215
• DOI: 10.1248/bpb.b15-00371

Pomegranate seed oil (PSO) has diverse bioactivities. It was hyphothesized that if PSO were employed to construct a trans-resveratrol-loaded self-nanoemulsifying drug delivery system (RES SNEDDS-PSO), not only could PSO serve as an oil phase but also exert synergistic effects with resveratrol to yield better therapeutic outcomes. In this study, we prepared RES SNEDDS-PSO for the first time to validate that hypothesis. The anti-inflammatory and anticancer activities of RES SNEDDS-PSO were compared with another SNEDDS composed of oil phase isopropyl palmitate (RES SNEDDS-IP). The results showed that upon exposure to a 10-fold amount of water, RES SNEDDS-PSO was converted into nanoemulsions with a mean size of 44 nm. Nanoemulsions enhanced the water solubility of resveratrol by 20-fold, significantly improved resveratrol stability in intestinal fluid, and slowed the decomposition of resveratrol in water by 1-fold. An in vivo anti-infection test showed that the degree of inflammatory swelling in mice given RES SNEDDS-PSO was only 60 and 76% that of the group fed with RES SNEDDS-IP at doses of 10 and 20 mg/kg, respectively. An in vitro anticancer study showed that the inhibitory rate of RES SNEDDS-PSO against MCF-7 breast cancer cells was 2.03- and 1.24-fold that of RES SNEDDS-IP at a concentration of 12.5 and 25 µg/mL, respectively. This study demonstrated that the newly developed SNEDDS may be a prospective formulation in the functional food and clinical fields.