Characterization, pharmacokinetics, and hypoglycemic effect of berberine loaded solid lipid nanoparticles.

The high aqueous solubility, poor permeability, and absorption of berberine (BBR) result in its low plasma level after oral administration, which greatly limits its clinical application. BBR solid lipid nanoparticles (SLNs) were prepared to achieve improved bioavailability and prolonged effect. Developed SLNs showed homogeneous spherical shapes, small size (76.8 nm), zeta potential (7.87 mV), encapsulation efficiency (58%), and drug loading (4.2%). The power of X-ray diffraction combined with (1)H nuclear magnetic resonance spectroscopy was employed to analyze chemical functional groups and the microstructure of BBR-SLNs, and indicated that the drug was wrapped in a lipid carrier. Single dose (50 mg/kg) oral pharmacokinetic studies in rats showed significant improvement (P<0.05) in the peak plasma concentration, area under the curve, and variance of mean residence time of BBR-SLNs when compared to BBR alone (P<0.05), suggesting improved bioavailability. Furthermore, oral administration of both BBR and BBR-SLNs significantly suppressed body weight gain, fasting blood glucose levels, and homeostasis assessment of insulin resistance, and ameliorated impaired glucose tolerance and insulin tolerance in db/db diabetic mice. BBR-SLNs at high dose (100 mg/kg) showed more potent effects when compared to an equivalent dose of BBR. Morphologic analysis demonstrated that BBR-SLNs potentially promoted islet function and protected the islet from regeneration. In conclusion, our study demonstrates that by entrapping BBR into SLNs the absorption of BBR and its anti-diabetic action were effectively enhanced.

Comparison of toxicokinetic and tissue distribution of triptolide-loaded solid lipid nanoparticles vs free triptolide in rats.

The traditional Chinese medicine Tripterygium wilfordii Hook F (TWHF) is used clinically to treat some autoimmune and inflammatory disorders including rheumatoid arthritis, systemic lupus erythematosus, and skin diseases. However TWHF has a high potential for toxicity, so its clinical use is limited. Solid lipid nanoparticle (SLN) delivery systems are reported to have remarkable advantages over conventional formulations of bioactive plant extracts, such as enhancing solubility and bioavailability, offering protection from toxicity, and enhancing pharmacological activity. We reported previously that a tripterygium glycoside (TG) solid lipid nanoparticle (TG-SLN) delivery system had a protective effect against TG-induced male reproductive toxicity. To better understand this issue, we used triptolide (TP) as a model drug in a comparative study of the toxicokinetic and tissue distribution of TP-SLN and free TP in rats, allowing us to observing the in vivo behavior of this nanoformulation and to assess mechanisms of SLN-related toxicity. A fast and sensitive HPLC-APCI-MS/MS method was developed for the determination of triptolide in rat plasma. Fourteen rats were divided randomly into two groups of 7 rats each for toxicokinetic analysis, with one group receiving free TP (450µg/kg) and the other receiving the TP-SLN formulation (450µg/kg). Blood was obtained before dosing and 0.083, 0.17, 0.25, 0.33, 0.5, 0.75, 1, 1.5, 2, 3 and 4h after drug administration. Thirty-six rats were divided randomly into six equal groups for a tissue-distribution study. Half of the rats received intragastric administration of TP (450µg/kg) and the other half received TP-SLN (450µg/kg). At 15, 45, and 90min after dosing, samples of blood, liver, kidney, spleen, lung, and testicular tissue were taken. TP concentration in the samples was determined by LC-APCI-MS-MS. The toxicokinetic results for the nanoformulation showed a significant increase the area under the curve (AUC) (P<0.05), significantly longer T(max) and mean retention times (MRTs) (0-t) (P<0.05), significantly decreased C(max) (P<0.05). The nanoformulation promoted absorption with a slow release character, indicating that toxicokinetic changes may be the most important mechanism for the enhanced efficacy of nanoformulations. Tissue-distribution results suggest a tendency for TP concentrations in the lung and spleen to increase, while TP concentrations in plasma, liver, kidney, and testes tended to decrease in the TP-SLN group. At multiple time points, testicular tissue TP concentrations were lower in the TP-SLN group than in free TP group. This provides an important clue for the decreased reproductive toxicity observed with TP-SLN.