Enhanced absorption of hydroxysafflor yellow A using a self-double-emulsifying drug delivery system: in vitro and in vivo studies

Abstract

Hydroxysafflor yellow A (HSYA), the main active ingredient of the safflower plant (Carthamus tinctorius L.), is a hydrophilic drug with low oral bioavailability. Water-in-oil-in-water (w/o/w) double emulsions may enhance the oral absorption of HSYA. In this study, we prepared a selfdouble-emulsifying drug delivery system (SDEDDS) to improve the absorption of HSYA. SDEDDS consists of water in oil emulsions and hydrophilic surfactants that can self-emulsify into w/o/w double emulsions in the aqueous gastrointestinal environment. Confocal laser scanning micrographs showed that spherical droplets were uniformly distributed in the dispersion medium with narrow particle size distribution and could form fine w/o/w double emulsions upon dilution in dispersion medium with gentle stirring. The dispersed oil droplets contained small dispersed aqueous droplets consistent with the characteristics of double emulsions. Furthermore, in vitro cellular experiments were performed to study the mechanism of the absorption promoting effect of SDEDDS. The accumulation of rhodamine-123 in Caco-2 cells was used to evaluate the efflux transport of p-glycoprotein inhibitor. Histopathologic studies on the rat intestine showed that SDEDDS can cause mucosal damage to a certain degree of toxicity, however this was not serious. These results suggest that SDEDDS can greatly improve the oral absorption of HSYA. Given the toxicity demonstrated to the small intestine, the formulation prescription should be improved to enhance security in the future.

Hydroxysafflor Yellow A: A Systematical Review on Botanical Resources, Physicochemical Properties, Drug Delivery System, Pharmacokinetics, and Pharmacological Effects

“…The study demonstrated that SDEDDS significantly improved the permeability of HSYA through Caco-2 cells monolayers, and plasma concentration increased by 2.17 times. The apparent permeability coefficient (Papp) of HSYA and HSYA-SDEDDS were (3.52 ± 1.41) × 10 −6 cm/s and (6.62 ± 2.61) × 10 −6 cm/s at the same concentrate (0.4 mg/ml), which improved to 1.88-fold by SDEDDS (Lv et al, 2012).…”

Pharmacological Actions, Molecular Mechanisms, Pharmacokinetic Progressions, and Clinical Applications of Hydroxysafflor Yellow A in Antidiabetic Research

“…Some oral delivery systems of HSYA are shown in Figure 3 . They are water-in-oil microemulsion [ 65 ], self-double-emulsifying [ 66 ], hydrophobic nanoparticles [ 67 ], chitosan complex [ 68 ], solid lipid nanoparticles [ 69 ], and natural deep eutectic solvents [ 70 ].…”

“…Some oral delivery systems of HSYA are shown in Figure 3. They are water-in-oil microemulsion [65], self-double-emulsifying [66], hydrophobic nanoparticles [67], chitosan complex [68], solid lipid nanoparticles [69], and natural deep eutectic solvents [70]. Related research suggested that shell nanoparticles are a highly effective delivery system for resveratrol, another natural compound, due to their significant effects in increasing the bioavailability and anti-inflammation activity [71].…”

Therapeutic Potential of Hydroxysafflor Yellow A on Cardio-Cerebrovascular Diseases

“…However, among many administration routes, oral administration is of great significance in drug formation because of its convenience and safety. Thus, the microemulsion, nanoemulsion, and nanoparticles of HSYA have been developed to overcome the low oral bioavailability (Li et al, 2010;Qi et al, 2011;Lv et al, 2012;Shi et al, 2018;Zhao B. X. et al, 2018). Considering the weak ability of HSYA to penetrate the BBB in physiologic condition (He et al, 2008), Borneolum Syntheticum and Acori Talarinowii Rhizoma were used to enhance its BBB permeability (Wu et al, 2011).…”