Preparation and characterization of nimodipine-loaded nanostructured lipid systems for enhanced solubility and bioavailability.

PURPOSE: Nimodipine (NMP) is a clinical dihydropyridine calcium antagonist. However, the clinical application of NMP is limited by poor water solubility and low oral bioavailability. To overcome these drawbacks, this study designed optimal NMP-incorporated nanostructured lipid carriers (NLCs). METHODS: High-pressure homogenization was successfully applied to prepare NMP-NLC, and the nanoparticle morphology was observed by a transmission electron microscope. The existence form of NMP in NMP-NLC was investigated by powder X-ray diffraction, differential scanning calorimetry, and Fourier transform infrared spectroscopy, respectively. The in vitro release study was performed by the dialysis method, and in vivo studies including in situ intestinal perfusion and pharmacokinetics were investigated in rats with NMP detected by high-performance liquid chromatography. RESULTS: The obtained NMP-NLC shared a spherical shape of ~70 nm with a smooth surface and high encapsulation efficiency of 86.8%±2.1%. Spectroscopy indicated that the drug was in an amorphous state. The NMP-NLC exhibited a sustained release and diverse release profiles under different release medium, which mimicked the physiological environment. Moreover, an in situ intestinal perfusion experiment revealed that NMP-NLC could be mainly absorbed by the small intestine. Remarkable improvements in Cmax and AUC0-∞ from NMP-NLC were obtained from pharmacokinetic experiments, and the relative bioavailability of NMP-loaded nanostructured lipid systems was 160.96% relative to NMP suspensions. CONCLUSION: Collectively, the NLCs significantly enhanced the oral bioavailability of NMP and might provide a promising nanoplatform for hydrophobic drug delivery.

Antiviral activity of baicalin against influenza A (H1N1/H3N2) virus in cell culture and in mice and its inhibition of neuraminidase.

Scutellaria baicalensis Georgi, a Chinese herbal decoction, has been used for the treatment of the common cold, fever and influenza virus infections. In previous studies, we found that oral administration of baicalein resulted in the inhibition of influenza A virus replication in vivo, which was linked to baicalin in serum. However, the effective dose and underlying mechanisms of the efficacy of baicalin against influenza A virus have not been fully elucidated. In this study, the antiviral effects of baicalin in influenza-virus-infected MDCK cells and mice were examined. The neuraminidase inhibition assay was performed to investigate the mechanism of action of baicalin. In vitro results showed that baicalin exhibited a half-maximal effective concentration (EC50) of 43.3 µg/ml against the influenza A/FM1/1/47 (H1N1) virus and 104.9 µg/ml against the influenza A/Beijing/32/92 (H3N2) virus. When added to MDCK cell cultures after inoculation with influenza virus, baicalin demonstrated obvious antiviral activity that increased in a dose-dependent manner, indicating that baicalin affected virus budding. Baicalin had clear inhibitory effects against neuraminidases, with half-maximal inhibitory concentration (IC50) of 52.3 µg/ml against the influenza A/FM1/1/47 (H1N1) virus and 85.8 µg/ml against the influenza A/Beijing/32/92 (H3N2) virus. In vivo studies showed that an intravenous injection of baicalin effectively reduced the death rate, prolonged the mean day to death (MDD) and improved the lung parameters of mice infected with influenza A virus. These results demonstrate that baicalin acts as a neuraminidase inhibitor, with clear inhibitory activities that are effective against different strains of influenza A virus in both cell culture and a mouse model, and that baicalin has potential utility in the management of influenza virus infections.

[HPLC-ELSD fingerprint of Marsdenia tenacissima from different habitats].

OBJECTIVE: To establish a HPLC-ELSD fingerprint of Marsdenia tenacissima from different habitats, in order to provide a reliable method for scientific assessment and effective quality control. METHOD: HPLC-ELSD was adopted to determine 25 baches of M. tenacissima herbs from different habitats. Traditional Chinese medicine chromatographic fingerprint similarity software assessment system 2004 developed by China Pharmacopoeia Committee was adopted to establish a common mode chart and assess chromatographic similarity based on the degree of correlation. RESULT: The common mode for M. tenacissima herb C21 steroidal fingerprint was established, including 11 common characteristic peaks. Among them, 10 were identified. According to the assessment on the similarity of 25 batches of samples, 80% of them showed a similarity of over 0.80 in steroidal HPLC-ELSD fingerprint. CONCLUSION: The method can be used to assess the quality of M. tenacissima.