Preparation of rosiglitazone maleate sustained-release floating microspheres for improved bioavailability.

The object of this study was to prepare rosiglitazone maleate (RM) sustained-release floating microspheres and investigate their pharmacokinetics. RM microspheres were prepared with ethyl cellulose (EC) and octadecyl alcohol as the carrier materials by an emulsion-solvent diffusion method, and the properties of morphology in vitro floating capability, drug loading (DL), entrapment efficiency (EE), in vitro release and in vivo pharmacokinetics were investigated. The prepared microspheres had a completely spherical shape. The percentage of microspheres floating after 12 h was (91.45 +/- 1.62)%, and the DL and EE were (9.31 +/- 0.31)% and (89.55 +/- 1.65)% respectively. Pharmacokinetic studies demonstrated that the RM floating microspheres were superior to commercial tablets in terms of the decrease in peak plasma concentration and maintenance of RM concentration in plasma. The area under the curve of plasma concentration-time (AUC) of the floating microspheres was equivalent to that of reference tablets. The results showed that floating microspheres are a feasible approach for the sustained-release preparation of drugs which have limited absorption sites in the upper small intestine.

Injectable hydrogel helps bone marrow-derived mononuclear cells restore infarcted myocardium.

BACKGROUNDS: Experimental and clinical studies have suggested that cell implantation could improve cardiac function after myocardial infarction (MI). However, this technique was limited by decreased engraftment and survival of transplanted cells within the ischemic tissue. The present study was performed to investigate whether implantation of bone marrow-derived mononuclear cells (BMMNCs) encapsulated in hydrogel could increase cell engraftment and help to restore cardiac function of MI rabbits. METHODS: MI was induced in rabbits by coronary artery ligation. One week later, cell culture medium, Dex-PCL-HEMA/PNIPAAm hydrogel, BMMNCs in medium or BMMNCs in hydrogel were injected into the infarcted area of the left ventricle (LV). RESULTS: Increased cell engraftment was observed 48 h after injection when cells were encapsulated in hydrogel; 30 days after treatment, echocardiographic studies showed that injection of BMMNCs in hydrogel preserved LV ejection fraction and attenuated LV dilatation compared with other groups. Histological analysis indicated that injection of BMMNCs in hydrogel enhanced neovascular formation and prevented scar expansion compared with the other groups. CONCLUSION: Injection of hydrogel-encapsulated BMMNCs increased cell engraftment and improved LV function; this technique may serve as an effective approach to restore infarcted myocardium.

Decreased infiltration of macrophages and inhibited activation of nuclear factor-kappa B in blood vessels: a possible mechanism for the anti-atherogenic effects of losartan.

UNLABELLED: Short-term administration of losartan reduced the aortic surface lesion area and mean intimal thickness. The mechanisms for reducing atherosclerotic progression by losartan may be related to decreased macrophage proliferation and accumulation in the arterial wall, decreased activation of nuclear factor-kappa B and expression of its target gene ICAM-I. OBJECTIVE: Recent studies suggest that angiotensin II (Ang II) may contribute to the vascular inflammatory response and atherosclerosis. Losartan is a specific AT1 receptor antagonist which can effectively inhibit the effects of Ang II. However, the effects of losartan on atherogenesis have been rarely demonstrated. We designed this study to investigate the effects of short-term administration of losartan on atherosclerotic lesions in the aorta from rabbits fed a cholesterol-enriched diet and the possible mechanisms of its anti-atherogenic effects. METHODS AND RESULTS: The rabbits were randomly divided into three groups: (a) cholesterol group; (b) losartan-treated group; (c) normal control group. We observed that mean serum lipid levels in the cholesterol group were significantly higher than those in normal control rabbits, while blood pressure between two groups did not change significantly. Treatment with losartan did not affect serum lipid levels or systolic blood pressure but did reduce the aortic surface lesion area and mean intimal thickness. The number of macrophages markedly decreased after administration of losartan. Losartan also attenuated the activation of nuclear factor-kappa B and the expression of its target gene ICAM-I. CONCLUSIONS: In summary, losartan inhibited atherosclerotic progression by decreasing macrophage proliferation and accumulation in the arterial wall. The mechanisms for reducing atherosclerotic progression by losartan may be related to decreased activation of nuclear factor-kappa B.