Stability of hepatoprotecting agent IFC-305 encapsulated into sol-gel titania nanoparticles and drug release evaluation: water and drug concentration effect.

IFC-305 was encapsulated into nanostructured titania and functionalized with OH groups by the sol-gel process using titanium n-butoxide, to be used in a drug delivery system for the treatment of liver cancer. Synthesis was carried out at different molar hydrolysis ratios: 4, 8, 16 and 24 mol of water; and drug concentration of 10, 20 and 30%. Characterization of IFC-titania reservoirs was carried out by Fourier transformed infrared spectroscopy (FTIR), X-ray diffraction (XRD), thermal analysis (DTA-TGA), scanning electron microscopy (SEM), and N2 adsorption-desorption isotherms (BET), confirms that IFC-305 is entrapped and stabilized in the TiO2-OH matrix. Drug liberation in vitro was determined by UV spectrometry over a period of 1000 h. This study demonstrated that the higher water content and the higher amount of loaded IFC, favored hydrogen bonding between titania-OH surface and IFC-NH groups, increasing the rate of drug release.

Comparison of nanostructured titania matrices obtained by carbon template and sol-gel methods for controlled release of fluoxetine.

Two types of titania matrix were investigated as a support for the prolonged drug delivery of the antidepressant fluoxetine. Sample MT was synthesized using carbon template and consisted of titania microtubes on which then fluoxetine was adsorbed. Sample SG was synthesized by the sol-gel method when the drug was added during the reaction. The morphology of the powder surfaces was found to be different: nanotubes versus almost spherical particles with much larger surface area of SG and smaller pores. The relative degrees of hydroxyl coverage of the surface were studied by FTIR-spectroscopy and were found to be much larger for the sol-gel complex. Theoretical modeling was applied to consider possible interactions between the drug and the matrices. The liberation of the drug was proved to be faster from complex MT and was attributed to weaker drug-matrix interactions in combination with larger pore size.

Functional role of the calmodulin- and inositol 1,4,5-trisphosphate receptor-binding (CIRB) site of TRPC6 in human platelet activation.

BACKGROUND: All identified mammalian TRPC channels show a C-terminal calmodulin (CaM)- and inositol 1,4,5-trisphosphate receptors (IP(3)Rs)-binding (CIRB) site involved in the regulation of TRPC channel function. OBJECTIVES: To assess the basis of CaM/IP(3)Rs binding to the CIRB site of TRPC6 and its role in platelet physiology. METHODS: Protein association was detected by co-immunoprecipitation and Western blotting, Ca(2+) mobilization was measured by fluorimetric techniques and platelet function was analyzed by aggregometry. RESULTS: Co-immunoprecipitation of TRPC6 with CaM or the IP(3)Rs at different cytosolic free Ca(2+) concentrations ([Ca(2+)](c)) indicates that the association between these proteins is finely regulated by cytosolic Ca(2+) via association of CaM and displacement of the IP(3)Rs at high [Ca(2+)](c). Thrombin-stimulated association of TRPC6 with CaM or the IP(3)Rs was sensitive to 2-APB and partially inhibited by dimethyl BAPTA loading, thus suggesting that the association between these proteins occurs through both Ca(2+)-dependent and -independent mechanisms. Incorporation of an anti-TRPC6 C-terminal antibody, whose epitope overlaps the CIRB region, impaired the dynamics of the association of TRPC6 with CaM and the IP(3)Rs, which lead to both inhibition and enhancement of thrombin- and thapsigargin-evoked Ca(2+) entry in the presence of low or high, respectively, extracellular Ca(2+) concentrations, as well as altered thrombin-evoked platelet aggregation. CONCLUSIONS: Our results indicate that the CIRB site of TRPC6 plays an important functional role in platelets both modulating Ca(2+) entry and aggregation through its interaction with CaM and IP(3)Rs.

Sympathetic skin response in hemodialysis patients: correlation with nerve conduction studies and adequacy of dialysis.

A sympathetic skin response (SSR) test was performed in diabetic and nondiabetic patients undergoing regular hemodialysis and the results correlated with nerve conduction studies (NCS): sensory conduction velocity (SCV) and motor conduction velocity (MCV). Comparisons were made between diabetic and nondiabetic patients and between cuprophane and polyacrylonitrile membrane dialyzed patients. Six nondiabetic uremic patients (30%) and all diabetic patients had no SSR. Eight nondiabetic uremic patients (40%) had a mildly impaired response. Nondiabetic patients with a normal response were younger (31.1+/-16.4 years) than the patients with abnormal SSR, whether mildly impaired response (58.3+/-20.3 years; p<0.05, Anova) or absent response (65.3+/-13.8 years; p<0.01, Anova). SCV, MCV, and SSR values were reduced (p<0.01) in uremic patients with respect to normal subjects. Severity and frequencies of sensory NCS abnormalities in nondiabetic patients were: normal 20%, mildly impaired 75%, and severely impaired 5%. Severity and frequencies of motor conduction abnormalities were: normal 80%, mildly impaired 20%, severely impaired 0%. The SSR abnormality incidence in patients with a normal NCS was similar to that in patients with either mildly or severely impaired NCS (chi-square test). There was a positive linear correlation between the SSR amplitude and SCV (r = 0.52, p<0.01) and MCV (r = 0.49, p<0.01). The SSR latency was also significantly related to SCV (r = 0.66, p<0.01) and MCV (r = 0.61, p<0.01). A significant negative correlation was found between age and SSR parameters, amplitude (r = -0.56, p<0.01) and latency (r = -0.66, p<0.01). No correlation was found between duration of hemodialysis or Kt/V and SSR. No differences were found in SSR, NCS, or Kt/V values between cuprophane membrane and polyacrylonitrile membrane dialyzed patients (Student's t test). The relationship between NCS and SSR in uremic patients was confirmed. Old age and diabetes mellitus, but not the dialysis membrane used, were confirmed as synergistic factors of neuropathic impairment. It appeared that SSR is more sensitive than NCS in detecting polyneuropathy in uremic patients on hemodialysis.