Luminescence functionalization of SBA-15 by YVO4 : Eu3+ as a novel drug delivery system

Luminescence functionalization of the ordered mesoporous SBA-15 silica was realized by depositing a YVO4:Eu3+ phosphor layer on its surface via the Pechini sol-gel process, resulting in the formation of the YVO4:Eu3+@SBA-15 composite material. This material, which combines the mesoporous structure of SBA-15 and the strong red luminescence property of YVO4:Eu3+, can be used as a novel functional drug delivery system. The structure, morphology, porosity, and optical properties of the materials were well characterized by X-ray diffraction, Fourier transform infrared spectroscopy, scanning electron microscopy, transmission electron microscopy, N-2 adsorption, and photoluminescence spectra. As expected, the pore volume, surface area, and pore size of SBA-15 decrease in sequence after deposition of the YVO4:Eu3+ layer and the adsorption of ibuprofen (IBU, drug). The IBU-loaded YVO4:Eu3+@SBA-15 system still shows the red emission of Eu3+ (617 nm, D-5(0)-F-7(2)) under UV irradiation and the controlled drug release property. Additionally, the emission intensity of Eu3+ increases with an increase in the cumulative released amount of IBU in the system, making the extent of drug release easily identifiable, trackable, and monitorable by the change of luminescence. The system has great potential in the drug delivery and disease therapy fields.

MCM-41 functionalized with YVO4 : Eu3+: a novel drug delivery system

Luminescence functionalization of ordered mesoporous MCM-41 silica was realized by depositing a YVO4:Eu3+ phosphor layer on its surface via the Pechini sol-gel process. This material, which combines the mesoporous structure of MCM-41 and the strong red luminescence property of YVO4: Eu3+, has been studied as a host carrier for drug delivery/release systems. The structure, morphology, texture and optical properties of the materials were well characterized by x-ray diffraction ( XRD), Fourier infrared spectroscopy ( FT-IR), transmission electron microscopy ( TEM), N-2 adsorption and photoluminescence ( PL) spectra. The results indicated that the specific surface area and pore volume of MCM-41, which were directly correlated to the drug-loading amount and ibuprofen ( IBU) release rate, decreased in sequence after deposition of YVO4:Eu3+ and loading of IBU as expected. The IBU-loaded YVO4:Eu3+@ MCM-41 system still showed red luminescence under UV irradiation ( 365 nm) and a controlled release property for IBU. In addition, the emission intensity of Eu3+ increases with an increase in the cumulative released amount of IBU, making the extent of drug release easily identified, tracked and monitored by the change of luminescence, which demonstrates its potential application in drug delivery/release systems.

Daunomycin binding to detergent micelles: A model system for evaluating the hydrophobic contribution to drug-DNA interactions

The interaction of daunomycin with sodium dodecyl sulfate and Triton X-100 micelles was investigated as a model for the hydrophobic contribution to the free energy of DNA intercalation reactions. Measurements of visible absorbance, fluorescence lifetime, steady-state fluorescence emission intensity, and fluorescence anisotropy indicate that the anthraquinone ring partitions into the hydrophobic micelle interior. Fluorescence quenching experiments using both steady-state and lifetime measurements demonstrate reduced accessibility of daunomycin in sodium dodecyl sulfate micelles to the anionic quencher iodide and to the neutral quencher acrylamide. Quenching of daunomycin fluorescence by iodide in Triton X-100 micelles was similar to that seen with free daunomycin. Studies of the energetics of the interaction of daunomycin with micelles by fluorescence and absorbance titration methods and by isothermal titration calorimetry in the presence of excess micelles revealed that association with sodium dodecyl sulfate and Triton X-100 micelles is driven by a large negative enthalpy. Association of the drug with both types of micelles also has a favorable entropic contribution, which is larger in magnitude for Triton X-100 micelles than for sodium dodecyl sulfate micelles.

Drug-human serum albumin binding studied by capillary electrophoresis with electrochemiluminescence detection

A new technique for investigating drug-protein binding was developed employing capillary electrophoresis (CE) coupled with tris(2,2'-bipyridyl) ruthenium(II) [Ru(bPY)(3)(2+)] electrochemiluminescence (ECL) (CE-ECL) detection after equilibrium dialysis. Three basic drugs, namely pridinol, procyclidine and its analogue trihexyphenidyl, were successfully separated by capillary zone electrophoresis with end-column Ru(bPY)(3)(2+) ECL detection. The relative drug binding to human serum albumin (HSA) for each single drug as well'as for the three drugs binding simultaneously was calculated. It was found that the three antiparkinsonian drugs compete for the same binding site on HSA. This work demonstrated that Ru(bPY)(3)(2+) CE-ECL can be a suitable technique for studying drug-protein binding.

Biodegradable electrospun fibers for drug delivery

The influences of surfactants and medical drugs on the diameter size and uniformity of electrospun poly(L-lactic acid) (PLLA) fibers were examined by adding various surfactants (cationic, anionic, and nonionic) and typical drugs into the PLLA solution. Significant diameter reduction and uniformity improvement were observed. It was shown that the drugs were capsulated inside of the fibers and the drug release in the presence of proteinase K followed nearly zero-order kinetics due to the degradation of the PLLA fibers. Such ultrafine fiber mats containing drugs may find clinical applications in the future.

Determination of five pharmacologically active compounds extracted from Rhodiola for natural product drug discovery with HPLC-APCI-MS

A rapid and sensitive liquid chromatography-atmospheric pressure chemical ionization mass spectrometry (HPLC-APCI-MS) assay for the determination of five pharmacologically active compounds (PAC) extracted from the traditional Chinese medicine, Rhodiola , namely salidroside, tyrosol, rhodionin, gallic acid, and ethyl gallate has been developed. In this method, PAC could be baseline separated and detected with DAD at 275 nm. The validation of the method, including sensitivity, linearity, repeatability, and recovery, was examined. The linear calibration curves were acquired with correlation coefficient >0.999 and the limits of detection LOD (at a signal-to-noise ratio=3:1) were between 0.058 and 1.500 mu mol/L. It was found, that the amounts of PAC varied with different species of Rhodiola . The established method is rapid and reproducible for the separation of five natural pharmacologically active compounds from extracts of Rhodiola with satisfactory results.

Analysis of five pharmacologically active compounds from Rhodiola for natural product drug discovery with capillary electrophoresis

A rapid capillary electrophoresis method for the separation of five natural pharmacologically active compounds from extracted Rhodiola, namely salidroside, tyrosol, rhodionin, gallic acid and ethyl gallate has been developed. The separation of five natural pharmacologically active compounds was carried out in a fused-silica capillary with 14 mM boric acid, 30 mM SDS and 2.5% acetonitrile, adjusted to pH 10.7 with NaOH. Applied potential was 21 kV. The temperature of the capillary was maintained at 25 degreesC by the instrument thermostating system, with the correlation coefficients of 0.9805-0.9989 for migration time, and relative standards of < 3.52% for peak areas. The established method is rapid and reproducible for the separation of five natural pharmacologically compounds from extracts of Rhodiola with satisfactory results.

Drug-protein interaction studied by technique of microdialysis combined with high performance liquid chromatography

Drug-protein binding is an important process in determining the activity and fate of a pharmaceutical agent once it has entered the body. This review examines the method of microdialysis combined with high-performance liquid chromatography (HPLC) that has been developed;by ours to study such interactions, in which the microdialysis was applied to sample the free drug in the mixed solution of drug with protein, and HPLC to quantify the concentration of free drug in the microdialysate. This technique has successfully been used for determining various types of binding interactions between the low affinity drugs, high affinity drugs and enantiomers to HSA. For the case of competitive binding of two drugs to a protein in solution, a displacement equation has been derived and examined with four nonsteroidal anti-inflammatory drugs and HSA as model drugs and protein, respectively. Microdialysis with HPLC was adopted to determine simultaneously the free solute and displacing agent in drug-protein solutions. The method is able to locate the binding site and determine affinity constants even up to 10(7) L/mol accurately.

Study of interaction between drug enantiomers and serum albumin by capillary electrophoresis

The interaction between drugs and human serum albumin (HSA) was investigated by capillary electrophoresis (CE). It involves stereoselectivity, drug displacement and synergism effects. Under protein-drug binding equilibrium, the unbound concentrations of drug enantiomers were measured by frontal analysis (FA). The stereoselectivity of verapamil (VER) binding to HSA was proved by the different free fractions of two enantiomers. In physiological pH (7.4, ionic strength 0.17 phosphate buffer) when 300 mu M (+/-) VER were equilibrated with 500 mu M HSA, the concentration of unbound S-VER was about 1.7 times its antipode. The binding constants of two enantiomers, KR-VER and KS-VER, were 2670 and 850 M-1, respectively. However, no obvious stereoselective binding of propranolol (PRO) to HSA was observed. Trimethyl-beta-cyclodextrin (45 mM) was used as a chiral selector in pH 2.5 phosphate buffer. Several drug systems were studied by the method. When ibuprofen (IBU) was added into VER-HSA solution. R-VER was partially displaced while S-VER was not displaced at all. A binding synergism effect between bupivacaine (BUP) and verapamil was observed and further study suggested that verapamil and bupivacaine occupy different binding site of HSA (site II and site III, respectively).

Application of liquid pre-column capillary electrophoresis technique to the study of interaction between drug enantiomers and human serum albumin

Based on the chiral separation of several basic drugs, dimetindene, tetryzoline, theodrenaline and verapamil, the liquid pre-column capillary electrophoresis (LPC-CE) technique was established. It was used to determine free concentrations of drug enantiomers in mixed solutions with human serum albumin (HSA). To prevent HSA entering the CE chiral separation zone, the mobility differences between HSA and drugs under a specific pH condition were employed in the LPC. Thus, the detection confusion caused by protein was totally avoided. Further study of binding constants determination and protein binding competitions was carried out. The study proves that the LPC technique could be used for complex media, particularly the matrix of protein coexisting with a variety of drugs.

海洛因成瘾脑灰质密度和结构网络研究

Behavioral and functional imaging studies consistently show that heroin abuse leads to various cognitive impairments, while brain structural changes associated with heroin use remain poorly understood. In the current study, we used voxel-based morphology (VBM), a method sensitive to structural changes of the brain, to investigate the gray concentration in MRI structure images of heroin addicts. Results show that the concentration of the temporal cortex and frontal cortex of heroin users significantly decreased as compared to age/education matched normal controls. Further analysis revealed that this brain structure change was detectable only in the users who had used heroin more than 5 year, but not in the remaining users. These results converge to the abnormality of the brain structure in heroin users and this abnormality is clearly associated with duration of drug use. We then analyzed the large-scale brain structure network in the heroin addicts. As compared to the normal controls, there was significant difference in interregional correlation between the temporal cortex, hippocampus, thalamus, and frontal cortex. Importantly, two major indices of the small-world properties, Clustering coefficient(Cp) and shortest path length (Lp), which are thought to reflect the local specialty and global integrity, were marginal-significantly larger than the normal controls, especially for Lp. These results suggest that chronic use of heroin results in the reorganization of the brain system. Taken together, this thesis has provided compelling evidence for brain structure impairments in chronic heroin users and further characterized the large-scale brain structure network in the same population.