Heparinized polyvinyl alcohol to specifically adsorb low-density lipoprotein from plasma.

INTRODUCTION: A medical adsorbent for blood purification was developed to specifically adsorb low-density lipoprotein (LDL) from hypercholesterolemia patient's plasma by covalently immobilizing heparin onto the surface of polyvinyl alcohol (PVA) with the couplant toluence-2,4-diisocyanate (TDI). METHODS: We used IR to demonstrate the success of covalently immobilizing heparin onto the surface, and investigated its adsorption of LDL, and primarily evaluated its hemo-compatibility using tests for platelet adhesion, the degree of platelet activation and a hemolysis test. RESULTS: (1) Heparin was successfully covalently immobilized onto the surface, the maximum amount of heparin immobilized on the surface of 1g PVA-1799 granules was about 5 µg; (2) one optimal condition for adsorption of LDL from hyperlipidemia plasma was a pH within the range of 7.2∼9.5, accordingly the adsorptive ratio (adsorbent/g: plasma/L=1:2) for LDL was about 70%; (3) it exhibited good hemo-compatibility. CONCLUSION: The adsorbent results in satisfactory adsorption of LDL with good hemo-compatibility; it could potentially be used as a blood purification material, and immobilization of heparin onto medical materials may be a way to develop an LDL-specific adsorbent for blood purification.

Toxic effects of T-2 toxin on reproductive system in male mice.

The present study was conducted to evaluate the effects of T-2 toxin on semen quality, fertility and serum testosterone concentration in mice. Adult male mice were mated with sexually mature untreated female mice after being exposed to intraperitoneal injection of T-2 toxin at 0, 5, 10 or 15 mg/kg body weight daily for 7 successive days. Semen quality, serum testosterone concentration and fertility of treated mice were assessed. The results showed that the number of abnormal spermatozoa increased significantly and a significant decrease in spermatozoa with integrated acrosome was observed in males treated with T-2 toxin at all doses, As well, the amount of live spermatozoa decreased significantly in mice treated with 10 and 15 mg/kg body weight T-2 toxin. Low pregnancy rate and high fetal resorption rate were observed when females were mated with T-2 toxin-exposed males. Testicular and cauda epididymal sperm counts, efficiency of sperm production and serum testosterone concentration were significantly reduced in mice treated with T-2 toxin at all doses in a dose-dependent manner. In conclusion, these findings indicated that T-2 toxin presented toxic effects on reproductive system of adult male mice.

Preparation and Evaluation of Upconversion Nanoparticles Based miRNA Delivery Carrier in Colon Cancer Mice Model.

Therapeutic efficacy of solid tumor is often severely hampered by poor penetration of therapeutics into diseased tissues and lack of tumor targeting. In this study, the functionalized upconversion nanoparticles (UCNP)-based delivery vector targeting cancer cells was developed. Firstly, NaYF4:Yb/Tm (UCNP) was prepared with the solvothermal method for the uniform nanoparticle size and brilliant lattice structure. The SiO2 coated UCNP was demonstrated a high upconversion emission and good monodispersity, which was coupled with polyetherimide (PEI) and miR-145 vector. Then, it was further functionalized via hyaluronic acid (HA) (UCNP/PEI/HA Nanocomplex, UCNPs) coating for the targeted delivery and improved biocompatibility. The UCNPs/miR-145 displays an excellent biocompatibility, a high level of cellular uptake and miR-145 expression, which results in a significant cell cycle arrest in G1, and induces CCND1, CDK6 and CCNE2 proteins downregulation. In vivo, the HA-coated UCNPs were enriched at the tumor site by targeting and retention effects, which resulted in a significant inhibition of tumor growth. Histological experiments demonstrated that UCNPs did not show significant toxicity in mice colon cancer model. Taken together, a UCNPs-based delivery platform was successfully constructed and used for miRNA target delivery, which provided a new method and idea for bioengineering and nanotechnology-based tumor therapy.

Synergistic effects of polymer adsorbents on the performance of bilirubin hemoperfusion.

Neonatal hyperbilirubinemia (jaundice) is a common disease with high incidence. Currently, the clinical inefficiency of adult bilirubin hemoperfusion medical adsorbent is a major technical barrier for the application of hemoperfusion treatment to rescue the severe neonatal jaundice. Based on the well-known principle of synergistic effects, a series of customized bilirubin polymeric compounds, comprised of one or more of the following components (glycidyl methacrylate, sodium acrylate, methacrylic acid isooctyl, hexamethylene diamine, albumin), were designed and fabricated based on molecular design. Their adsorption performances upon bilirubin were investigated and compared under the same conditions, and the compound with the highest adsorption performance was then subject to preliliminary safety assessments and compared with a commercial one (BS330). The results showed that positive synergistic effects appeared on the adsorption performance to adsorb bilirubin based on this study, and the one comprised of glycidyl methacrylate+sodium acrylate+methacrylic acid isoocty+hexamethylene diamine+albumin possesses the highest adsorption performance as well as outome clinical acceptable medical safety assessments, and its adsorption efficiency was up to 46% while the commerical one's was about 26% under the same conditions. This study sheds a new light on how to design and develop hemoperfusion bilirubin adsorbents with good overall clinical performance, as well as providing a novel idea and experimental referrences for future related topics.

Preparation of heparin-immobilized PVA and its adsorption for low-density lipoprotein from hyperlipemia plasma.

In this study, heparin was covalently coupled by glutaraldehyde to Poly(vinyl alcohol) [PVA] in solid-liquid two-phase reaction system by two-step synthesis method to prepare a LDL-selective adsorbent. The parameters (the material ratio, reaction time and dosage of catalyzer) were investigated to evaluate their effect upon the immobilized amount of heparin onto the surface of PVA, IR was used to verify the covalent immobilization result and the heparin-modified PVA was also undergone the evaluation of its adsorption capability for low-density lipoprotein from hyperlipemia plasma, and its hemocompatibility was preliminarily evaluated by platelet adhesion test. Results showed: (1) under optimized reaction conditions the highest immobilization amount of heparin onto PVA surface within the experiments of this study has been obtained; (2) the optimized reaction conditions were: (i) at the refluxing temperature 78 degrees C; (ii) the material ratio of "PVA(g): 50% glutaraldehyde (ml)" was about "1:3"; (iii) the reaction time was about 5 h; and (iv) the amount of catalyzer (concentrated HCL) was about 1% of the 50% glutaraldehyde; (3) within the experiments of this study the highest immobilization amount would be up to 25 microg heparin on the surface of per g PVA granules; (4) the heparin-modified PVA granules showed significant adsorption for LDL under faintly alkaline environment (pH=7.2-9.5) ; (5) The result of platelet adhesion test showed no platelet adhered to its surface. Therefore, immobilization of heparin onto the surface of a support is one approach to prepare a kind of LDL adsorbent for blood purification.