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

Abstract

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.Key words pomegranate seed oil; self-nanoemulsification; trans-resveratrol; anti-inflammation; anticancer activity trans-Resveratrol (RES), a natural component, possesses broad therapeutic activities in the treatment of cancer, 1,2) inflammation, 3,4) neurodegenerative disorders, 5) hyperlipemia, 6) and so on. 7) However, trans-resveratrol application in clinic is scare due to its poor water-solubility, short half-life of 109 min, 8) and undesirable oral bioavailability. 9) In vivo, RES quickly conjugated with endogenous glucose acid or sulfuric acid at 3-position to convert into the metabolites, 3-monoglucuronide and 3-monosulfate.8) Strategies regarding innovative formulations have to be under consideration to overcome shortages of RES.Self-nanoemulsifying drug delivery system (SNEDDS) may be a promising vehicle to ameliorate oral bioavailability of RES. SNEDDS is a transparent, thermodynamically stable system, usually composed of oil, surfactant, and co-solvent. It rapidly forms oil in water (o/w) nanoemulsions when diluted with gastrointestinal (GI) fluid. 10) As SNEDDS has nano size and much larger surface area, it is able to notably enhance the dissolution of drug. High surface area of nanoemulsions also provides better interaction between drug and GI fluid, resulting in improved absorption as well as bioavailability.11) Long chain triglycerides, capryol 90, labrafac PG, and so on, are often employed as oil phases of SNEDDS.12) Though those oil phases are excellent candidates to produce SNEDDS in line with treatment requirements, owing to the lack of bi...

Pomegranate seed oil nanoemulsions with selective antiglioma activity: optimization and evaluation of cytotoxicity, genotoxicity and oxidative effects on mononuclear cells

“…There are few reports showing PSO nanoemulsions preparation, employing different methods as sonication (Mizrahi et al 2014), self-nanoemulsifying (Lu et al 2015), ultrasonic emulsification/solvent evaporation (Baccarin & Lemos-Senna 2014;Baccarin et al 2015aBaccarin et al , 2015b. Recently, our group developed PSO nanoemulsion by nanoemulsification, employing pullulan as stabilizer (Ferreira et al 2015).…”

Possible use of Punica granatum (Pomegranate) in cancer therapy

“…The PSO extract showed a synergistic effect with trans-resveratrol in a self-nanoemulsifying drug delivery system (RES SNEDDS). In vitro studies have found that RES SNEDDS-PSO has a remarkable inhibitory effect against MCF-7 breast cancer cells [93]. It has also been found that the mono-dispersed gold nanoparticles synthesized with pomegranate fruit peel extract (PAuNPs) improved the therapeutic potential of Fluorouracil and targeted drug delivery [94].…”

Current application of phytocompound-based nanocosmeceuticals for beauty and skin therapy

“…However, this method has limitations in cosmeceutical production due to instability of emulsions during storage. [149][150][151][152][153][154][155][156][157][158] Further, the emulsion core compounds direct whether a single or multiple nanoemulsions can be formed based on their number of core compounds in the nanosized emulsions. 159,160 Multiple emulsions have advantages over single emulsions, due to their wider applications in cosmeceuticals, which can further reduce cosmeceutical cost.…”