1.Multivalent hyaluronic acid bioconjugates improve sFlt-1 activity in vitro.
Altiok EI1, Santiago-Ortiz JL2, Svedlund FL3, Zbinden A1, Jha AK1, Bhatnagar D1, Loskill P4, Jackson WM1, Schaffer DV5, Healy KE6. Biomaterials. 2016 Mar 12;93:95-105. doi: 10.1016/j.biomaterials.2016.03.017. [Epub ahead of print]
Anti-VEGF drugs that are used in conjunction with laser ablation to treat patients with diabetic retinopathy suffer from short half-lives in the vitreous of the eye resulting in the need for frequent intravitreal injections. To improve the intravitreal half-life of anti-VEGF drugs, such as the VEGF decoy receptor sFlt-1, we developed multivalent bioconjugates of sFlt-1 grafted to linear hyaluronic acid (HyA) chains termed mvsFlt. Using size exclusion chromatography with multiangle light scattering (SEC-MALS), SDS-PAGE, and dynamic light scattering (DLS), we characterized the mvsFlt with a focus on the molecular weight contribution of protein and HyA components to the overall bioconjugate size. We found that mvsFlt activity was independent of HyA conjugation using a sandwich ELISA and in vitro angiogenesis assays including cell survival, migration and tube formation. Using an in vitro model of the vitreous with crosslinked HyA gels, we demonstrated that larger mvsFlt bioconjugates showed slowed release and mobility in these hydrogels compared to low molecular weight mvsFlt and unconjugated sFlt-1.
2.Clinical Drug-Drug Pharmacokinetic Interaction Potential of Sucralfate with Other Drugs: Review and Perspectives.
Sulochana SP1, Syed M2, Chandrasekar DV1, Mullangi R1, Srinivas NR3. Eur J Drug Metab Pharmacokinet. 2016 Apr 16. [Epub ahead of print]
Sucralfate, a complex of aluminium hydroxide with sulfated sucrose, forms a strong gastrointestinal tract (GIT) mucosal barrier with excellent anti-ulcer property. Because sucralfate does not undergo any significant oral absorption, sucralfate resides in the GIT for a considerable length of time. The unabsorbed sucralfate may alter the pharmacokinetics of the oral drugs by impeding its absorption and reducing the oral bioavailability. Because of the increased use of sucralfate, it was important to provide a reappraisal of the published clinical drug-drug interaction studies of sucralfate with scores of drugs. This review covers several category of drugs such as non-steroidal anti-inflammatory drugs, fluoroquinolones, histamine H2-receptor blockers, macrolides, anti-fungals, anti-diabetics, salicylic acid derivatives, steroidal anti-inflammatory drugs and provides pharmacokinetic data summary along with study design, objectives and key remarks.
3.Accelerating full thickness wound healing using Collagen Sponge of Mrigal Fish (Cirrhinus cirrhosus) scale Origin.
Pal P1, Srivas PK1, Dadhich P1, Das B1, Maity PP1, Moulik D2, Dhara S3. Int J Biol Macromol. 2016 Apr 13. pii: S0141-8130(16)30340-3. doi: 10.1016/j.ijbiomac.2016.04.032. [Epub ahead of print]
The potentiality of collagen sponge as a skin substitute, derived from mrigal (Cirrhinus cirrhosus) scale has been explored in this study. Acid soluble collagen (ASC) and pepsin soluble collagen (PSC) from the scale of mrigal were isolated and characterized. The yields of ASC and PSC were ∼3% and ∼7% based on the dry weight of scale while the hydroxyproline content was ∼90mg/g. Scanning electron microscope revealed progressive demineralization with EDTA on time dependent scale. Further, the D-Spacing in fibril bundles were calculated to be ∼67nm. Fourier transform infrared and circular dichroism spectra confirmed extracted protein to be collagen I, where both ASC and PSC comprised of two different α-chains (α1 and α2). The denaturation temperature (Td) of the collagen solution was 35°C closer to Td of mammalian collagen. In vitro cell culture studies on the extracted collagen sponge showed efficient cell growth and proliferation. Additionally, co-culture with fibroblast and keratinocyte cells showed development of stratified epidermal layer in vitro.
4.Antihyperlipidemic and Antioxidant Activities of Edible Tunisian Ficus carica L. Fruits in High Fat Diet-Induced Hyperlipidemic Rats.
Belguith-Hadriche O1,2, Ammar S3,4, Contreras MD4, Turki M5, Segura-Carretero A4, El Feki A6, Makni-Ayedi F5, Bouaziz M7. Plant Foods Hum Nutr. 2016 Apr 16. [Epub ahead of print]
The phenolic constituents of the aqueous-ethanolic extract of Tunisian Ficus carica (F. carica) fruit (FE) and its antihyperlipidemic and antioxidant activities in high-fat diet-induced hyperlipidemic rats (HFD) were evaluated. The obtained results demonstrated that the FE improved the lipid profile by decreasing the total cholesterol, triglyceride, low-density lipoprotein cholesterol and increasing high-density lipoprotein cholesterol levels. It also reduced the content of thiobarbituric acid-reactive substances and increased the antioxidant enzymes in liver, heart and kidney in HFD-fed rats. These antihyperlipidemic effects and in vivo antioxidative effects correlated with the in vitro phenolic content scavenging ability. Thus, the major phenolic compounds were identified using reversed-phase ultra-high-performance liquid chromatography (RP-UHPLC) coupled with two detection systems: diode-array detection (DAD) and quadrupole time-of-flight (QTOF) mass spectrometry (MS).