Influence of Polysorbate 60 on Formulation Properties and Bioavailability of Morin-Loaded Nanoemulsions with and without Low-Saponification-Degree Polyvinyl Alcohol

Abstract

The aim of the present study was to investigate the influence of polysorbate 60 (Tween 60) on the development of morin-loaded nanoemulsions to improve the oral bioavailability of morin. Nanoemulsions were prepared using Tween 60 and polyvinyl alcohol (PVA) as emulsifiers, and medium chain triglycerides (MCT) as the lipid base. Low-saponification-degree PVA (LL-810) was also added to stabilize dispersed droplets. MCT-LL810 nanoemulsion containing LL-810 was prepared with a reduced amount of Tween 60. However, the area under the blood concentration-time curve (AUC) of MCT-LL810 (0.18) nanoemulsion containing a small amount of Tween 60 did not increase because the absorption of morin was limited by P-glycoprotein (P-gp)-mediated efflux. MCT-LL810 (0.24) nanoemulsion containing a large amount of Tween 60 showed the highest AUC, dispersed droplets containing Tween 60 may have been transported into epithelial cells in the small intestine, and P-gp transport activity appeared to be suppressed by permeated Tween 60. Based on the plasma concentration profile, dispersed droplets in MCT-LL810 (0.24) nanoemulsion permeated more rapidly through the mucus layer and the intestinal membrane than MCT (0.24) nanoemulsion without LL-810. In conclusion, a novel feature of Tween 60 incorporated into the dispersed droplets of a nanoemulsion interacting with P-gp was demonstrated herein. Dispersed droplets in MCT-LL810 (0.24) nanoemulsion containing LL-810 permeated rapidly through the mucus layer and intestinal membrane, and Tween 60 incorporated in dispersed droplets interacted with P-gp-mediated efflux, increasing the bioavailability of morin.Key words nanoemulsion; morin; polyvinyl alcohol; bioavailability; P-glycoprotein Morin (2′,4′,3,5,7-pentahydroxyflavonoid) is one of the flavonoids widely found in fruits, vegetables, tea, and numerous therapeutic herbs.1) Its wide spectrum of biological activities, including anti-inflammatory, anti-cancer, antioxidant, antiangiogenic, anti-hypertensive, and anti-clastogenic activities, have been reported. [2][3][4][5][6][7][8] We previously demonstrated that a treatment with morin induced basal nitric oxide production and rapid improvements in endothelial function in diabetic mice.9) Morin has been suggested to improve the development of endothelial dysfunction by diabetes. However, the absolute bioavailability of morin after its oral administration is very low (less than 1%), and this may be attributed to its low aqueous solubility, P-glycoprotein (P-gp)-mediated efflux, and low intestinal permeability. [10][11][12] Various approaches have been attempted in order to increase the area under the blood concentration-time curve (AUC) of low bioavailability drugs after their oral administration. Nanoemulsion systems have received increasing attention as appropriate carriers for insoluble active compounds to increase bioavailability and modify drug release characteristics. [13][14][15] Improvements in the solubility of drugs into nanoemulsion components such as the oil phase and surfactants repre...

Lipid-Based Nanoparticles for Drug/Gene Delivery: An Overview of the Production Techniques and Difficulties Encountered in Their Industrial Development

“…53 To stabilize these small droplets, different types of emulsifiers, such as surfactants, phospholipids, proteins, polysaccharides or polymers such as poly(vinyl alcohol), can be added during the synthesis procedure. 54,55 These surfactants, whether ionic or nonionic, prevent droplet aggregation through electrostatic repulsion or steric hindrance, hydration, and thermal fluctuation interactions. 55,56 Nanoemulsions have a colloidal structure that enables solubilization and encapsulation of hydrophobic drugs, reducing adverse effects.…”

“…Nanoemulsions can be prepared as oil-in-water (o/w) or water-in-oil (w/o) droplets to carry either hydrophobic or hydrophilic active compounds, respectively . To stabilize these small droplets, different types of emulsifiers, such as surfactants, phospholipids, proteins, polysaccharides or polymers such as poly­(vinyl alcohol), can be added during the synthesis procedure. , These surfactants, whether ionic or nonionic, prevent droplet aggregation through electrostatic repulsion or steric hindrance, hydration, and thermal fluctuation interactions. , …”

“…54,55 These surfactants, whether ionic or nonionic, prevent droplet aggregation through electrostatic repulsion or steric hindrance, hydration, and thermal fluctuation interactions. 55,56 Nanoemulsions have a colloidal structure that enables solubilization and encapsulation of hydrophobic drugs, reducing adverse effects. 57 They are mainly used for topical drug delivery (Table 1) but have potential for other modes of administration like intravenous, ocular, intranasal, and oral delivery.…”

Andrographolide/Phospholipid/Cyclodextrin Complex-Loaded Nanoemulsion: Preparation, Optimization, <i>in Vitro</i> and <i>in Vivo</i> Evaluation

“…Recently, nanoemulsion (NE) has been reported as an excellent drug delivery system for drug efficiency enhancement. 9) Specifically, the solubility can be greatly improved since the drug-loaded droplets could disperse in the continuous phase through the nanotechnology. Further, the encapsulation of the continuous phase can make the drug release slowly, which is beneficial to achieve long-acting effects due to the sustained-release properties can prevent the drug from being prematurely released and destroyed by gastric fluid or enzymes.…”