SYNTHESIS AND CHARACTERIZATION OF NOVEL SA-PA-LSA/C-30B/AG NANOCOMPOSITES FOR SWELLING, ANTIBACTERIAL, DRUG DELIVERY, AND ANTICANCER APPLICATIONS

 Objective: The main objective of this work was to formulate and evaluate Closite-30B/nanoAg filled hydrogel composites which are further intentended to be used for the study of drug delivery,antibacterial, and anticancer activityMethods: In this study, Cloisite-30B (C-30B) clay dispersed biopolymer sodium alginate (SA)-grafted-poly (acrylamide [AAm]-co-lignosulfonic acid) hydrogel composites were synthesized by free radical in situ polymerization reaction technique using SA, AAm, and lignosulfonic acid biopolymers in different proportions in combination. which are subjected to invitro drug delivery and Minimum inhibitory concentration(MIC) method for antibacterial activity study by using Streptococcus faecalis (S.faecalis) and Escherichia coli (E. coli)bacteria. The biocompatibility of the prepared gels were determined by standard protocol HaCaT-cells and MCF-7 cell lines further the prepared hydrogel composites were characterized for particle size,encapsulation efficiency,swelling properties,compatibility studies by FTIR etc.Results: The formulated hydrogels were characterized by X-ray diffraction (XRD) to analyze the particles size and crystallinity. The presence of functional groups and their chemical interaction with the drug, C-30B, and silver nanoparticles (AgNPs) were confirmed by the FTIR spectroscopy. Furthermore, the presence of AgNPs in the matrix was confirmed by ultraviolet/visible spectroscopy. Thermogravimetric analysis was performed to find out the thermal degradation, thermal stability, and the percentage of weight loss at various temperatures. Swelling studies revealed that C-30B and AgNPs induced composites exhibited higher swelling ratio than pure hydrogels. The hydrogels with C-30B/AgNPs displayed excellent antibacterial activity against both Gram-positive and Gram-negative bacteria. Further, these hydrogel composites were loaded with the drug paclitaxel (PT), and drug release study showed that the sustained release of the drug from C-30B/Ag hydrogel matrix compared to rest of other samples. Hydrogel composites were cytocompatible in nature (with HaCaT cells) and the cell viability decreased (with MCF-7cells) with the presence of lignosulfonic acid as well as C-30B and AgNPs in the samples as evaluated through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide to its insoluble formazan assay.Conclusion: The synthesized hydrogel composites were successfully characterized and eavaluated for sustained release of paclitaxel drug delivery at different pHs and temperatures and it is found that C30B/Ag filled composites exhibits contolled release of drug with higher rate, especially at lower pH (pH2) and higher temperature (37oC) and the same formulations which exhibits better anitbcterial and anticancer activity compared to the virgin samples So the prepared C30B/AgNPs hydrogels composites used in drug dlivery for the effective treatment of cancer and used against bacterias and cancerous cells

Drug-Coated Versus Plain Balloon Angioplasty In Arteriovenous Fistulas : A Randomized, Controlled Study With 1-Year Follow-Up (The Drecorest Ii-Study)

Background and Aims: Stenosis due to intimal hyperplasia and restenosis after initially successful percutaneous angioplasty are common reasons for failing arteriovenous fistulas. The aim of this study was to evaluate the effect of drug-coated balloons in the treatment of arteriovenous fistula stenosis. Design: Single-center, parallel group, randomized controlled trial. Block randomized by sealed envelope 1:1. Materials and Methods: A total of 39 patients with primary or recurrent stenosis in a failing native arteriovenous fistulas were randomized to drug-coated balloon (n=19) or standard balloon angioplasty (n=20). Follow-up was 1year. Primary outcome measure was target lesion revascularization. Results: In all, 36 stenoses were analyzed; three patients were excluded due to technical failure after randomization. A total of 88.9% (16/18) in the drug-coated balloon group was revascularized or occluded within 1year, compared to 22.2% (4/18) of the stenoses in the balloon angioplasty group (relative risk for drug-coated balloon 7.09). Mean time-to- target lesion revascularization was 110 and 193days after the drug-coated balloon and balloon angioplasty, respectively (p=0.06). Conclusions: With 1-year follow-up, the target lesion revascularization-free survival after drug-coated balloon-treatment was clearly worse. The reason for this remains unknown, but it may be due to differences in the biological response to paclitaxel in the venous arteriovenous fistula-wall compared to its antiproliferative effect in the arterial wall after drug-coated balloon treatment of atherosclerotic occlusive lesions. Trial registration: ClinicalTrials.gov NCT03036241Peer reviewe

Proposta de sistemas embarcados para identificação de buracos em rodovias utilizando as Leis da Mecânica de Newton

Mainly in Brazilian streets, drivers needs to be careful, not only in traffic, but also in holes in the road. Due lack the supervision and the difficult to map these holes, responsible companies not always perform the maintenance. With a system to identify and map the holes, these companies can take an action before the quality of the road becomes impassable. Thus, this paper propose to develop an embedded system to identify holes in the road using the laws of classical Newtonian mechanic

Pancreatic Tumor Microenvironmental Acidosis and Hypoxia Transform Gold Nanorods Into Cell-Penetrant Particles for Potent Radiosensitization

Coating nanoparticles with stealth epilayers increases circulation time by evading opsonization, macrophage phagocytosis, and reticuloendothelial sequestration. However, this also reduces internalization by cancer cells upon reaching the tumor. We designed gold nanorods (GNRs) with an epilayer that retains stealth properties in circulation but transforms spontaneously in the acidotic tumor microenvironment to a cell-penetrating particle. We used a customized stoichiometric ratio of l-glutamic acid and l-lysine within an amphiphilic polymer of poly(l-glutamic acid-co-l-lysine), or P(Glu-co-Lys), to effect this transformation in acidotic environments. P(Glu-co-Lys)-GNRs were internalized by cancer cells to facilitate potent in vitro radiosensitization. When administered intravenously in mice, they accumulate in the periphery and core of tumors without any signs of serum biochemical or hematological alterations, normal organ histopathological abnormalities, or overt deterioration in animal health. Furthermore, P(Glu-co-Lys)-GNRs penetrated the tumor microenvironment to accumulate in the hypoxic cores of tumors to potently radiosensitize heterotopic and orthotopic pancreatic cancers in vivo

The type 2C phosphatase Wip1: An oncogenic regulator of tumor suppressor and DNA damage response pathways

The Wild-type p53-induced phosphatase 1, Wip1 (or PPM1D), is unusual in that it is a serine/threonine phosphatase with oncogenic activity. A member of the type 2C phosphatases (PP2Cδ), Wip1 has been shown to be amplified and overexpressed in multiple human cancer types, including breast and ovarian carcinomas. In rodent primary fibroblast transformation assays, Wip1 cooperates with known oncogenes to induce transformed foci. The recent identification of target proteins that are dephosphorylated by Wip1 has provided mechanistic insights into its oncogenic functions. Wip1 acts as a homeostatic regulator of the DNA damage response by dephosphorylating proteins that are substrates of both ATM and ATR, important DNA damage sensor kinases. Wip1 also suppresses the activity of multiple tumor suppressors, including p53, ATM, p16INK4a and ARF. We present evidence that the suppression of p53, p38 MAP kinase, and ATM/ATR signaling pathways by Wip1 are important components of its oncogenicity when it is amplified and overexpressed in human cancers

DEVELOPMENT, FORMULATION, AND EVALUATION OF SODIUM ALGINATE-G-POLY (ACRYL AMIDE-CO-ACRYLIC ACID/CLOISTE-30B)/AGNPs HYDROGEL COMPOSITES AND THEIR APPLICATIONS IN PACLITAXEL DRUG DELIVERY AND ANTICANCER ACTIVITY

Objective: The objective of this study was to develop, formulate and evaluate the sodium alginate grafted poly (acrylamide-co-acrylic acid/cloisite-30B/silver nanoparticle hydrogel composites (SA-PAAm-PAAc/C30B/AgNPs) with varying weight percentage (wt %) of cloisite-30B clay for paclitaxel targeted delivery and anticancer activity. Methods: Polymer hydrogel composites of different wt % of cloisite-30B modified clay dispersed sodium alginate (SA) grafted polyacrylamide-co-polyacrylic acid were prepared via in situ free radical initiation polymerization reaction technique. In vitro release of paclitaxel (PT) anticancer drug and anticancer studies were performed. The formulations were further evaluated for swelling, drug encapsulation, drug delivery, anticancer activity study, Fourier transforms infrared spectroscopy (FT-IR), thermogravimetric (TGA), differential scanning calorimeter (DSC) and x-ray diffraction (XRD) characterizations. Results: FT-IR spectroscopy of various composite hydrogel formulations displayed good compatibility between sodium alginate, polyacrylamide, and polyacrylic acid polymers. The thermal study reveals that the formulations with clay (C30B) and AgNPs in hydrogel composites exhibit good thermal stability and less % of weight loss (wt. loss) compared to pure formulations. Further, the highest encapsulation efficiency was shown by the formulation S0-0+D (72.66±5.92%) and least encapsulation efficiency was shown by S75Ag+D (41.33±3.12%) compared to rest of the formulations and S50Ag+D and S75Ag+D samples exhibits relatively slightly higher and sustained cumulative release rate of PT drug at an average rate of 80±9 % within 72 h and also shows relatively better anticancer activity compared to other formulations. Conclusion: Formulations S50Ag+D and S75Ag+Dwere found to be best formulations with a higher cumulative percentage of PT drug release and showed better anticancer activit

SYNTHESIS AND CHARACTERIZATION OF NOVEL SA-PA-LSA/C-30B/AG NANOCOMPOSITES FOR SWELLING, ANTIBACTERIAL, DRUG DELIVERY, AND ANTICANCER APPLICATIONS

 Objective: The main objective of this work was to formulate and evaluate Closite-30B/nanoAg filled hydrogel composites which are further intentended to be used for the study of drug delivery,antibacterial, and anticancer activityMethods: In this study, Cloisite-30B (C-30B) clay dispersed biopolymer sodium alginate (SA)-grafted-poly (acrylamide [AAm]-co-lignosulfonic acid) hydrogel composites were synthesized by free radical in situ polymerization reaction technique using SA, AAm, and lignosulfonic acid biopolymers in different proportions in combination. which are subjected to invitro drug delivery and Minimum inhibitory concentration(MIC) method for antibacterial activity study by using Streptococcus faecalis (S.faecalis) and Escherichia coli (E. coli)bacteria. The biocompatibility of the prepared gels were determined by standard protocol HaCaT-cells and MCF-7 cell lines further the prepared hydrogel composites were characterized for particle size,encapsulation efficiency,swelling properties,compatibility studies by FTIR etc.Results: The formulated hydrogels were characterized by X-ray diffraction (XRD) to analyze the particles size and crystallinity. The presence of functional groups and their chemical interaction with the drug, C-30B, and silver nanoparticles (AgNPs) were confirmed by the FTIR spectroscopy. Furthermore, the presence of AgNPs in the matrix was confirmed by ultraviolet/visible spectroscopy. Thermogravimetric analysis was performed to find out the thermal degradation, thermal stability, and the percentage of weight loss at various temperatures. Swelling studies revealed that C-30B and AgNPs induced composites exhibited higher swelling ratio than pure hydrogels. The hydrogels with C-30B/AgNPs displayed excellent antibacterial activity against both Gram-positive and Gram-negative bacteria. Further, these hydrogel composites were loaded with the drug paclitaxel (PT), and drug release study showed that the sustained release of the drug from C-30B/Ag hydrogel matrix compared to rest of other samples. Hydrogel composites were cytocompatible in nature (with HaCaT cells) and the cell viability decreased (with MCF-7cells) with the presence of lignosulfonic acid as well as C-30B and AgNPs in the samples as evaluated through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide to its insoluble formazan assay.Conclusion: The synthesized hydrogel composites were successfully characterized and eavaluated for sustained release of paclitaxel drug delivery at different pHs and temperatures and it is found that C30B/Ag filled composites exhibits contolled release of drug with higher rate, especially at lower pH (pH2) and higher temperature (37oC) and the same formulations which exhibits better anitbcterial and anticancer activity compared to the virgin samples So the prepared C30B/AgNPs hydrogels composites used in drug dlivery for the effective treatment of cancer and used against bacterias and cancerous cells