Preparation, In Vivo and In Vitro Evaluation, and Pharmacodynamic Study of DMY‐Loaded Self‐Microemulsifying Drug Delivery System

Abstract

Hyperlipidemia has become a common disease in modern society with its prevalence becoming relatively high in the world. A series of complications that accompany hyperlipidemia are seriously threatening individuals’ health. Dihydromyricetin (DMY) is a kind of polyphenol hydroxy (OH) dihydroflavonol extracted from the stems and leaves of Ampelopsis grossedentata. It has a variety of pharmacological activities. This study aims to develop a self‐microemulsifying drug delivery system (SMEDDS) to improve the oral bioavailability of DMY, and to evaluate its hypolipidemic activity. The self‐microemulsion drug delivery system is composed of medium chain triglyceride (MCT, oil phase), Tween 80 (emulsifier), and PEG 200 (coemulsifier). The prepared DMY‐SMEDDS has stable physical and chemical properties, small droplet size (15.49 ±0.15 nm), good polydispersity index (PDI = 0.160 ± 0.010), negative zeta potential (−17.37 ± 0.09 mV), and high encapsulation efficiency (98.04 ± 0.25%). The results of in vitro dissolution and in vivo pharmacokinetics show that the prepared DMY‐SMEDDS significantly improve the solubility of DMY in aqueous medium, while its oral bioavailability is 2.34 times higher than that of free drug. In conclusion, the DMY‐SMEDDS prepared in this study prospectively improves the solubility and oral bioavailability of DMY also enhance the therapeutic effect. Practical Applications: This study is relevant in the sense that SMEDDS may be used as a new strategy to improve the oral bioavailability of hydrophobic drugs. This novel nanocarrier could increase (by 2.34 times) the relative bioavailability of oral DMY‐SMEDDS in rats comparative to dihydromyricetin (DMY) suspension. Thus, DMY‐SMEDDS may prospectively be applied in food, nutraceutical, and pharmaceutical industries in view of its biocompatible excipients and good stability.

Medium-Chain Triacylglycerols (MCTs) and Their Fractions in Drug Delivery Systems : A Systematic Review

“…For the oral/enteral route, a study by Liu et al 31) showed that MCTs (RH40) produced a ZP value of −25 mV indicating a good colloidal stability. Another study by Luo et al 30) showed that the MCTs exhibited a ZP of −44.4 mV leading to an excellent stability, while those in a study by Wang et al 34) showed a ZP value of 17.37 mV. For the parenteral route, the MCTs in a research by Khan et al 40) showed a ZP of −22±1.5 mV leading to a moderate stability.…”

“…Another study by Wang et al 34) proposed the development of a self-microemulsifying drug delivery system (SMEDDS) to evaluate the oral bioavailability and hypolipidemic activity of dihydromyricetin (DMY) . The SMEDDS was composed of a caprylic oil phase, Tween 80 as an emulsifier, and PEG 200 as a co-emulsifier.…”

“…A PDI value of ＞0.5 may cause stability disruptions due to a higher possibility of particle coalescence 44) . For the oral/ enteral route, two out of nine articles were chosen to study the PDI values, and both studies showed a narrow size distribution of 0.160 31,34) . In contrast, Liu et al 31) showed that MCTs (RH40) produces a PDI value of ＜0.2.…”

“…In oral/enteral route, a study conducted by Lu et al 33) resulted in an EE of 81.5±3.5％ indicating that curcumin encapsulated in Pickering emulsions containing MCTs exhibit improved stability and drug release. Wang et al 34) concluded that the DMY-loaded self-microemulsion containing caprylic acid improves the poor water solubility and oral bioavailability of DMY as it exhibited an EE of 98.04±0.25％ and a DLC of 6.90±0.19％. A study by Zoubari et al 35) using topical route resulted in an EE of ＞ 80％ for both dexamethasone and diclofenac sodium drugs formulated with Capryol ® 90.…”

Vitexin loaded mixed polymeric micelles: preparation, optimization, evaluation and anti-osteoporotic effect

“…A drop of mixed micelle solution diluted to the appropriate concentration was placed on a copper grid covered with carbon film and negatively stained with phosphotungstic acid solution (2%, w v −1 ) for 30 s [34]. The morphology was observed by TEM after drying at room temperature.…”