Synthesis and Release of Dapsone-Alginate (DS-Alg) Conjugate / 中国药学杂志

OBJECTIVE: To synthesize and characterize dapsone-alginate acid (DS-ALG) conjugate. METHODS: Alginate (Alg) was selected as the drug carrier and valine (Val) as the linking arm to synthesize DS-Alg, which could be applied to topical administration. And the synthetic condition of DS-Alg was optimized by changing the amount of 1-(3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride (EDC) and N-hydroxysuccinimide (NHS), while the pH of solvent was changed in the range of 4.0 to 6.0. The structures of the products were characterized by 1H-NMR, MS and FT-IR. Meanwhile, the drug release in vitro of DS-Alg was investigated in the mixture of pH 7.4, 0.05 mol•L -1 PBS and ethanol by diffusion cells. The concentration of DS or valine-dapsone in the release medium was detected by HPLC. Taking rats with local scald as model, the drug release in vivo was measured by coating the trauma with DS-Alg conjugate cream and monitoring the drug concentration in blood. RESULTS: The optimum synthetic conditions of DS-Alg were as follows: 0.277 g valine-dapsone, 0.400 g sodium alginate, 7 eq EDC, 3 eq NHS, pH of the solvent of 5.5. And during 72 h, there was no DS detected in the release medium or rat plasma. The AUC0→72 h of DS-Alg was 0. It suggested that DS immobilized by Alg with covalent bond was too stable to be released from Alg in vitro and in vivo. The DS-Alg conjugate could effectively prevent DS from entering the systemic circulation. CONCLUSION: DS-Alg conjugate is successfully synthesized. The conjugate is stable that DS cannot be released from the conjugate to the bloodstream, which can efficiently decrease the side effects of DS and has the potential for topical administration.

A lipophilic prodrug of Danshensu: preparation, characterization, and in vitro and in vivo evaluation / 中国天然药物

Danshensu [3-(3, 4-dihydroxyphenyl) lactic acid, DSS], one of the significant cardioprotective components, is extracted from the root of Salvia miltiorrhiza. In the present study, an ester prodrug of Danshensu (DSS), palmitoyl Danshensu (PDSS), was synthesized with the aim to improve its oral bioavailability and prolong its half-life. The in vitro experiments were carried out to evaluate the physicochemical properties and stability of PDSS. Although the solubility of PDSS in water was only 0.055 mg·mL, its solubility in FaSSIF and FeSSIF reached 4.68 and 9.08 mg·mL, respectively. Octanol-water partition coefficient (log P) was increased from -2.48 of DSS to 1.90 of PDSS. PDSS was relatively stable in the aqueous solution in pH range from 5.6 to 7.4. Furthermore, the pharmacokinetics in rats was evaluated after oral administration of PDSS and DSS. AUC and t of PDSS were enhanced up to 9.8-fold and 2.2-fold, respectively, compared to that of DSS. C was 1.67 ± 0.11 μg·mL for PDSS and 0.81 ± 0.06 μg·mL for DSS. Thus, these results demonstrated that PDSS had much higher oral bioavailability and longer circulation time than its parent drug.

Study of flavanoids extracted from onion on the blood-brain barrier permeation and neuroprotective effects / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To study the flavanoids extracted from onion on the blood-brain barrier (BBB) permeation, and their effects on primary cultured neuron cell proliferation and apoptosis of SD rats using ethanol reflux method.</p><p><b>METHODS</b>The brain microvascular endothelial cells (BMVECs) were first successfully primary cultured. Then rats BMVECs and astrocytes (ACs) were co-cultured to establish the in vitro BBB model. The flavanoids were extracted from onion using ethanol reflux method. The model was verified by transmission electron microscopy (TEM) and trans-epithelial electric resistance (TEER). The flavanoids permeability was tested using high performance liquid chromatography (HPLC). Meanwhile, rat neuron cells were cultured and exposed to H2O2 and flavanoids. Their effects on the cell proliferation and apoptosis were observed using MTT assay. The injury of neuron DNA was analyzed using single-cell gel electrophoresis (SCGE) and immunofluorescent assay.</p><p><b>RESULTS</b>The in vitro BBB model was successfully established by TEM and TEER. Results of HPLC proved flavanoids extracts could effectively permeate the BBB with the permeability of 60.58%. The extractive at 10 - 20 microg/mL showed obvious inhibition on the apoptosis of neuron cells induced by H2O2, and attenuated the injury of neuron DNA.</p><p><b>CONCLUSIONS</b>The flavanoids extracted from onion ethanol reflux method could effectively penetrate the BBB. They also showed obvious inhibition on the H2O2 induced neuron cell apoptosis and DNA injury.</p>

Association of XPC and XPG polymorphisms with the risk of hepatocellular carcinoma / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate whether the polymorphism of DNA repair genes XPC (Ala499Val and Lys939Gln) and XPG (His1104Asp) is associated with the susceptibility to hepatocellular carcinoma (HCC).</p><p><b>METHODS</b>A hospital-based case-control study was conducted in 500 cases with HCC and 507 controls. Genotypes of XPC and XPG were determined by real-time polymerase chain reaction with the TaqMan MGB probe.</p><p><b>RESULTS</b>Compared to the CC genotype, the CT genotype and the TT genotype of XPC Ala499Val were not associated with the susceptibility to HCC (adjusted OR = 1.34, 95% CI: 0.85-2.12; adjusted OR = 1.30, 95% CI: 0.68-2.51, respectively). Compared to the AA genotype, the AC genotype and the CC genotype of Lys939Gln were not associated with the susceptibility to HCC (adjusted OR = 1.20, 95% CI: 0.78-1.85; adjusted OR = 1.81, 95% CI: 0.88-3.73, respectively). Compared to the CC genotype, the CG genotype and the GG genotype of XPG His1104Asp were not associated with the susceptibility to HCC (adjusted OR = 0.85, 95% CI: 0.56-1.27; adjusted OR = 1.12, 95% CI: 0.67-1.87, respectively) However, the stratified analysis revealed that the females with the AC+CC genotype of XPC Lys939Gln had increased risk of HCC compared to those with AA genotype (OR = 2.17, 95% CI: 1.01-4.64).</p><p><b>CONCLUSION</b>Our results suggest that XPC and XPG polymorphisms do not independently affect on the susceptibility to HCC, but the joint effect of C allele of XPC Lys939Gln and female may modify the risk of HCC.</p>