Enhanced absorption of hydroxysafflor yellow A using a self-double-emulsifying drug delivery system: in vitro and in vivo studies.
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 self-double-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.
Department of Pharmacy, Zhejiang Provincial People's Hospital, Zhejiang University, Hangzhou, China.
Liang-Zhong
LZ
Lv
Chen-Qi
CQ
Tong
Qing
Q
Lv
Xin-Jiang
XJ
Tang
Li-Ming
LM
Li
Qing-Xia
QX
Fang
Jia
J
Yu
Min
M
Han
Jian-Qing
JQ
Gao
D000042:Absorption; D000704:Analysis of Variance; D000818:Animals; D019540:Area Under Curve; D018938:Caco-2 Cells; D002470:Cell Survival / Q000187:drug effects; D002599:Chalcone / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems / Q000379:methods*; D004655:Emulsions / Q000737:chemistry; D006801:Humans; D007413:Intestinal Mucosa / Q000187:drug effects / Q000473:pathology; D008297:Male; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry*; D011809:Quinones / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D012235:Rhodamines / Q000737:chemistry / Q000493:pharmacokinetics
D004655:Emulsions; D011809:Quinones; D012235:Rhodamines; C085278:hydroxysafflor yellow A; D002599:Chalcone