Preparation of tanshinone Ⅱ_A-glycyrrhetinic acid solid lipid nanoparticles and its inhibitory effect on acne / 中国中药杂志

The optimal prescription of tanshinone Ⅱ_A(TSN)-glycyrrhetinic acid(GA) solid lipid nanoparticles(GT-SLNs) was explored and evaluated in vivo and in vitro, and its effect on acne after oral administration was investigated. The preparation processing and prescription were optimized and verified by single factor and response surface methodology. The in vitro release of GA and TSN in GT-SLNs was determined by ultra-performance liquid chromatography(UPLC). The effect of GT-SLNs on acne was investigated by the levels of sex hormones in mice, ear swelling model, and tissue changes in sebaceous glands, and the pharmacokinetics was evaluated. The 24-hour cumulative release rates of GA and TSN in SLNs were 65.87%±5.63% and 36.13%±2.31% respectively. After oral administration of GT-SLNs and the mixture of GA and TSN(GT-Mix), the AUC_(0-t) and AUC_(0-∞) of TSN in GT-SLNs were 1.98 times and 4.77 times those in the GT-Mix group, respectively, and the peak concentration of TSN in the GT-SLNs group was 17.2 times that in the GT-Mix group. After intragastric administration of GT-SLNs, the serum levels of testosterone(T) and the ratio of testosterone to estradiol(T/E2) in the GT-SLNs group significantly declined, and the sebaceous glands of mice were atrophied to a certain extent. The results demonstrated that obtained GT-SLNs with good encapsulation efficiency and uniform particle size could promote the release of GA and TSN. GT-SLNs displayed therapeutic efficacy on acne manifested by androgen increase, abnormal sebaceous gland secretion, and inflammatory damage.

Intestinal lymphatic transport of matrine from two self-nanoemulsifying drug delivery systems assessed by triple single pass intestinal perfusion approach in rats / 中国药学杂志

OBJECTIVE: To investigate the differences of two matrine (MA) self-nanoemulsifying drug delivery systems (SNEDDS) in intestinal lymphatic transport. METHODS: Triple single pass intestinal perfusion model (T-SPIP) was established to study the intestinal absorption kinetics of MA in different absorption segments of rats with chylomicron flow blocking approach using colchicine as the blocker. The concentration of MA in the perfustae was measured by HPLC. RESULTS: The two SNEDDSs had regular spherical surface and narrow particle size distribution. MA showed high Peff. The phospholipid complex formulation (MPC-SN) exhibited higher intestinal lymphatic transport especially in distal ileum, and it was influenced more significantly by the chylomicron flow blocker in distal ileum compared to in proximal jejunum and mid-small intestine. CONCLUSION: SNEDDS can improve the absorption of MA by intestinal lymphatic transport. MPC-SN might be easier to be absorbed via lymphatic transport because of its high lipophilicity and small particle size.

Enhancement of intestinal permeability of Quercetin by nanostructured lipid carriers / 中国药学杂志

OBJECTIVE: To elucidate biological characteristics and uptake mechanism of Quercetin-nanostructured lipid carriers (Q-S) in vivo and in vitro. METHODS: Quercetin suspension (Q-X), quercetin-phospholipid complex (Q-L) and nanostructured lipid carriers loaded with quercetin (Q-S) were prepared. Then the intestinal permeability of these three formulations were studied using in situ rat intestinal perfusion, followed by in vivo relative oral bioavailability studies. In addition, in vitro cellular uptake of quercetin from Q-S in a time and concentration-dependent were carried out. To elucidate the uptake mechanism(s) from Q-S, Q-L and Q-X contribution of NPCILI carrier-mediated uptake, endocytosis and passive permeability were investigated. RESULTS: In situ studies demonstrated Q-S has 14-fold higher permeability than Q-X and 3-fold than Q-L. In vivo studies showed Q-S relative oral bioavailability is increased dramatically (Fr=4.6), meanwhile, no significant increased for Q-L compared with Q-X. Consistent with in situ results, in vitro time and concentration-dependent studies revealed quercetin uptake from Q-S was obviously higher than Q-X and Q-L. In vitro mechanistic characterization showed that the reduced contribution of NPCILI to the transport and passive diffusion enhancement of quercetin are primary explanations for its enhanced uptake from Q-S. CONCLUSION: Quercetin can enhance oral bioavailability attributed to enhance passive permeability and reduce transport of NPCILI formed nanostructured lipid carriers.