ABSTRACT
The release attributes of anticancer therapeutic embedded in programmable gum ghatti hydrogel matrices has been evaluated. Hydrogel has been programmed simply by adjusting the product composition (monomer-acrylamide and crosslinker- N, N Methylenebisacrylamide (MBAm)) to control mesh size during copolymerization of gum through microwave based technique. The synthesized system has been characterized for physicochemical traits and 'in-vitro' drug release in various physiological pH conditions by USP standard method. The degree of crosslinking analysed through equilibrium swelling ratio (ESR) has been correlated with release kinetics. The release profiles yielded from the measurements of cumulative drug delivery showed that the system with lower ESR included slower release rate than that of the system with higher ESR, consequently generated higher t50 values. Additionally, the release rate rises with rise in pH milieu.
Subject(s)
Drug Carriers/chemistry , Drug Liberation , Fluorouracil/administration & dosage , Hydrogels/chemistry , Plant Gums/chemistry , Acrylamides/chemistry , Hydrogen-Ion Concentration , In Vitro Techniques , Microwaves , PolymerizationABSTRACT
For a newly synthesized compound, identifying its target protein is a slow but pivotal step toward understand its pharmacologic mechanism. In this study, we systemically synthesized novel manzamine derivatives and chose 1-(9'-methyl-3'-carbazole)-3, 4-dihydro-ß-carboline (MCDC) as an example to identify its target protein and function. MCDC had potent toxicity against several cancer cells. To identify its target protein, we first used a docking screen to predict macrophage migration inhibitory factor (MIF) as the potential target. Biochemical experiments, including mutation analysis and hydrogen-deuterium exchange assays, validated the binding of MCDC to MIF. Furthermore, MCDC was shown by microarrays to interfere with the cell cycle of breast cancer MCF7 cells. The activated signaling pathways included AKT phosphorylation and S phase-related proteins. Our results showed MIF as a potential direct target of a newly synthesized manzamine derivative, MCDC, and its pharmacologic mechanisms.
Subject(s)
Antineoplastic Agents/pharmacology , Breast Neoplasms/drug therapy , Carbazoles/pharmacology , Carbolines/pharmacology , Gene Expression Regulation, Neoplastic/drug effects , Intramolecular Oxidoreductases/antagonists & inhibitors , Macrophage Migration-Inhibitory Factors/antagonists & inhibitors , Antineoplastic Agents/chemistry , Apoptosis , Biomarkers, Tumor , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Carbazoles/chemistry , Carbolines/chemistry , Cell Cycle , Cell Proliferation , Female , Gene Expression Profiling , Humans , Intramolecular Oxidoreductases/metabolism , Macrophage Migration-Inhibitory Factors/metabolism , Phosphorylation , Tumor Cells, CulturedABSTRACT
The purpose of this study is to fabricate 5-Fluorouracil sustained release matrix based on a novel, nontoxic, eco-friendly modified biopolymer. The sesbania gum based hydrogel has been prepared by microwave assisted method using acrylamide as a monomer and N,N Methylenebisacrylamide as a crosslinker. The crosslink copolymerization has been confirmed by several modern techniques such as FTIR, SEM, XRD, TGA, DSC, elemental analysis etc. The bioactive 5-Fluorouracil has been encapsulated via solvent swelling method and its release rate has been investigated in various pH dissolution medium through USP standard protocol. The synthesized hydrogel with higher degree of crosslinking exhibited slower release rate than that of hydrogel having lower degree of crosslinking. Thus, resulting higher t25 value, the release rate increases with increase in pH of the medium. Release kinetics suggests the non-Fickian release behaviour of the hydrogel.
Subject(s)
Drug Carriers/chemistry , Drug Liberation , Fluorouracil/chemistry , Galactans/chemistry , Hydrogels/chemistry , Mannans/chemistry , Plant Gums/chemistry , Kinetics , Microwaves , SolubilityABSTRACT
This work describes the significance of graft copolymer induced flocculation process in sugarcane juice clarification. The naturally occurring cinnamic acid has been successfully incorporated into the structure of sesbania gum through microwave assisted technique (hybrid of conventional and microwave based method) to develop novel, non-toxic, eco-friendly product with highly extended structure. The customized structure of gum derivative has been characterized by a number of modern techniques like 13C NMR, FTIR, SEM, XRD, TGA, DSC, elemental and viscometric analysis. The separation of suspended colloidal impurities from cane juice has been achieved through the application of synthesized gum derivative as a flocculant. The clarification performance of the graft copolymer has been evaluated in terms of turbidity, absorbance, and degree brix (°bx). The flocculant exhibited maximum efficiency at 1.0ppm (optimized dose) without altering the nutritional parameters (% sugar content). The clarified juice thus obtained may be used as a beverage for direct consumption or for the manufacture of white sugar.
