Optimization and Characterization of Cuscuta reflexa Extract Loaded Phytosomes by the Box-Behnken Design to Improve the Oral Bioavailability

Abstract

The purpose of this study is to determine whether the complexing hydroalcoholic extract of Cuscuta reflexa (HECR) with phosphatidyl choline increases its bioavailability. As a result, a novel phytosomal delivery system for the HECR-soya lecithin complex was developed (HECR-phytosome). The HECR-phytosome complex was synthesized and characterized as phytovesicles. The formulation was prepared using a variable concentration of soya lecithin (1:1–1:3 percent w/v), a temperature range of (45-65℃), and sonication time (4-8 min). Optimization of HECR-loaded phytosomal formulations was performed using Design Expert software. A three-factor, three-level Box-Behnken design was used to optimize this HECR delivery system, as dependent variables, vesicular size and entrapment efficiency were evaluated using a Box Behnken factorial design. Further characterization of the optimized formulation included vesicle size, PDI, zeta potential, entrapment efficiency, FTIR, DSC, TEM, and in vitro release. Vesicle sizes ranged from 173.5±6.17 nm to 215.9±6.53 nm, and response rates for entrapment efficiency ranged from 52.9±1.65 to 77.2±1.1%. The uniform structure and spherical shape were demonstrated by transmission electron microscopy. Among the drug release kinetic models, the formulation followed the Higuchi model (R2 = 0.9978), releasing 96.3±3.7% of the polyphenol and flavonoids phytoconstituents from HECR-loaded phytosomes in 12 hours, compared to 49.3±2.5% in the plain extract. In addition, the optimized formulation passes the stability test. Therefore, the results demonstrated that phytosomal nanocarriers have the potential to increase the bioavailability of Cuscuta reflexa extract.