Nanoemulsion improves hypoglycemic efficacy of berberine by overcoming its gastrointestinal challenge.

Berberine (BBR) is an important natural product with poor gastrointestinal behavior includes low permeability, P-glycoprotein efflux, and mass elimination in the intestine. The aim of this study was to develop a novel nanoemulsion (NE) to improve the hypoglycemic efficacy of BBR. NE was prepared and characterized by morphology and droplet size detection, stored stability, in vitro intestinal lipolysis and metabolism, Caco-2 cells transport, in situ single-pass intestinal perfusion, oral bioavailability in rats, and hypoglycemic efficacy in high-fat diet and streptozocin-induced mice. BBR-loaded NE exhibits small droplet size (30.56 ±â€¯0.35 nm) and good stability. NE could remain intact after lipolysis and protect BBR against the intestinal metabolism mediated by CYP2D6 and CYP3A4. Cells transport and intestinal perfusion studies revealed that NE decreases the P-glycoprotein efflux of BBR by 2-fold and enhances its permeability by 5.5-fold. Consequently, NE increased the oral bioavailability of BBR in rats by 212.02%. Compared to BBR control, blood glucose level of diabetic mice by NE was decreased by 3-fold. This novel NE provides a promising carrier to improve the hypoglycemic efficacy of BBR by overcoming its gastrointestinal deficiency, which may offer a product for the therapy of diabetes.

[Drug delivery systems of baicalin, baicalin-phospholipid complex and self-microemulsifying drug across Caco-2 cell model].

OBJECTIVE: To study the absorption of baicalin (BA), baicalin-phospholipid complex (BA-PC), and two kinds of self-microemulsifying drug delivery system (SMEDDS) of BA-PC (BA-PC-NE-SMEDDS with natural emulsifier and BA-PC-NS-SMEDDS with nonionic surfactants) and predict the ability of improving bioavailability through changing the formulation of BA. METHODS: Transmembrane transports of each formulation were studied by Caco-2 cell model and the concentration of BA was determined by HPLC. RESULTS: With the increasing concentration of BA, the transport rate and apparent permeability coefficient (Papp) of BA was increased,indicating the passive absorption mechanism of BA. While with the increase of transport time, the transport rate and Papp of BA was decreased slowly, most likely due to the biological transformation of BA during the permeation process as reported in other people's paper. When coupled with P-gp inhibitor (Verapamil), the efflux rate (ER) of BA decreased from 2.07 to 0.48, indicating it was the substrate of P-gp. Compared with BA,the cumulative permeate quantity of BA-PC and BA-PC-SMEDDS were with no significant increase before 90 min (P > 0.05), but increased obviously after 90 min (P < 0.05). Three hours later, the cumulative permeate quantity and Papp showed significant differences (P < 0.05) among each formulation and were arranged in the following order: BA-PC-NS-SMEDDS > BA-PC-NE-SMEDDS > BA-PC > BA. Furthermore, the Papp of BA-PC and BA-PC-SMEDDS was significantly greater than that of BA coupled with Verapamil (P < 0.05). CONCLUSION: PC promotes the permeation of BA; PC-SMEDDS further accelerates its permeation bases on BA-PC; And BA-PC-NS-SMEDDS shows the better effect than BA-PC-NE-SMEDDS to promote the permeation of BA.

[Study on stability and cutaneous permeation kinetics in vitro of positive-ionized liposome gel containing paeonol].

OBJECTIVE: To prepare positive-ionized liposome gel containing paeonol and study its stability and cutaneous permeation kinetics in vitro. METHODS: Prepared the liposome gel by dispersion-ultrasonic and gridding method, and studied the stability with the impact factor experiments. Compared the permeation rate of liposome gel with conventional gel in vitro using the Franz-diffusion cell. RESULTS: Mean diameter of the liposome was (132.7 +/- 14.1) nm with Zeta potential of (+33.54 +/- 1.95) mV and mean entrapment efficiency of (73.04 +/- 1.24)% (n=3), and the content of paeonol was (3.17 +/- 0.13) mg/g (n=3). The liposome gel had a promising appearance. It was stable at the humidity and the room temperature while was sensitive at the light and the temperature from 40 degrees C to 60 degrees C. The cumulative penetration amounts of the liposome gel was higher than that of the conventional gel (P < 0.05). Its cutaneous penetration rate and cumulative amounts in skin were higher than those of the conventional gel (P < 0.05). CONCLUSION: The positive-ionized liposome gel containing paeonol is stable and feasibly prepared. It can enhance the cutaneous permeation efficiency and guarantee the persistent release rate.