Effect of age on the pharmacokinetics of polymorphic nimodipine in rats after oral administration.

The previous investigation has proved that their existed pharmacokinetic difference between the different crystal forms of the polymorphic drugs after oral administration. However, no systemic investigations have been made on the change of this pharmacokinetic difference, resulted either from the physiological or from the pathological factors. In this paper, we used polymorphic nimodipine (Nim) as a model drug and investigated the effect of age difference (2- and 9-month old) on the pharmacokinetics after oral delivery in rats. As the results shown, for L-form of Nim (L-Nim), the AUC0-24 h in 2-month-old rats was 343.68±47.15 ng·h/mL, which is 23.36% higher than that in 9-month-old rats. For H-form of Nim (H-Nim), the AUC0-24 h in 2-month-old rats was 140.91±19.47 ng·h/mL, which is 54.64% higher than that in 9-month-old rats. The AUC0-24 h ratio between H-Nim and L-Nim was 2.44 in 2-month-old rats and 3.06 in 9-month-old rats. Since age difference could result in unparallelled change of the absorption and bioavailability of the polymorphic drugs, the results in this experiment are of value for further investigation of crystal form selection in clinical trials and rational clinical application of the polymorphic drugs.

Inhibition of tumor metastasis in vivo by combination of paclitaxel and hyaluronic acid.

There is little information about the inhibitory effects of hyaluronic acid with paclitaxel on tumor metastasis and ascites formation. The aim of present study is to determine whether the combined administration of hyaluronic acid (HA) with paclitaxel can produce additional or synergistic therapeutic effects in the control of Lewis lung carcinoma (LLC) migration and ascites formation of U14 cervical tumor. The anti-metastasis effect of hyaluronic acid alone, paclitaxel alone and paclitaxel-hyaluronic acid combination were examined in a mouse model bearing LLC cells. i.v. Paclitaxel-hyaluronic acid, in the ratio of 1:3 (w/w), significantly reduced the migration of LLC cells in a synergistic fashion. In the experiment with mice bearing U14 tumor cells, i.p. paclitaxel-hyaluronic acid markedly improved the life span of mice and significantly decreased ascites formation when compared to paclitaxel alone or hyalunonan alone. We also analyzed the serum proteome of mice with lung neoplasm before and after treatment with paclitaxel-hyaluronic acid. Proteomic analysis on LLC mice was studied using two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) and mass spectrometry. The results showed that i.v. administration of hyaluronic acid in combination with paclitaxel had significantly up-regulated the expression of vitamin D(3) binding proteins (DBP), which is a macrophage-stimulating activator. In conclusion, the in vivo anti-metastasis effect was associated with the synergistic therapeutic effects of hyaluronic acid-paclitaxel combination and a significant promotion of immune proteins expression. These results demonstrated that the combination of paclitaxel and hyaluronic acid may be an effective way to inhibit tumor migration.

A fluorescence study of sodium hyaluronate/surfactant interactions in aqueous media.

The interactions between sodium hyaluronate, an anionic polysaccharide, with surfactants (anionic and nonionic) were investigated using pyrene fluorescence measurement methods. The change of micropolarity produced by the interaction was monitored by the measurement of emission intensity ratio between the first and third bands (I1/I3), and the intensity ratio of the excimer and the third vibration monomer band (I(E)/I(M)). Because the hydrophilic heads on the SDS were attracted by the domains formed by the hydroxyl groups of hyaluronate, the I1/I3 ratio was reduced by the addition of hyaluronate at lower than 0.06% of sodium dodecyl sulfate (SDS) concentration. No aggregation was observed between hyaluronate and nonionic surfactants (Tween-80 and Cremophor EL) in the whole concentration range studied. At a higher concentration of surfactant, the I1/I3 ratio of hyaluronate/surfactant was influenced by the addition of saccharide (glucose, lactose, or mannitol). However, the effect of saccharide could be reduced by the addition of salt.