Current Chemical Biology - Volume 11, Issue 1, 2017

Biodegradable and nontoxic natural biopolymers are commonly being studied as a potential carrier material for novel drug delivery system due to its bio-compatible nature. Hydrogels are hydrophilic cross-linked polymer networks. They are able to imbibe large amounts of water or biological fluids. Guar gum (GG) is a galactomannan. It is obtained from plant Cyamopsis Tetragonolobus Linn. It has wide applications in pharmaceutical formulations, cosmetic, food, textile, paper, explosive, toiletries industries, etc. However, due to uncontrollable rate of viscosity, uncontrollable rate of hydration, instability of its solution for a long time and susceptibility to microbial contamination restricts the use of GG in pharmaceutical industries. To overcome these drawbacks, GG should be modified to hydrogel. GG based hydrogels are widely used in pharmaceutical application due to its changes in physic-chemical properties. GG and its derivatives are used as binders, disintegrate in the formulation of tablets. They are also used as control-released agents in novel drug delivery. The present review has been aimed to give an overview of GG based hydrogels for pharmaceutical applications.

Commercially available, most important microbial polysaccharide is xanthan gum. In many pharmaceutical products and cosmetics, xanthan gum has been widely used as emulsifying and suspending agent. The gelatinous layer creates hinderance to the penetration of water, thereby slowing down the solubilization of the xanthan gum. Its less solubility in polar solvents, is limiting the application of xanthan gum in various drug delivery systems. Biocompatibility, abundance in nature and hydrogel’s similarity with biological systems; are the characteristics of polysaccharides to be chosen as suitable material for biomedical applications. One of the natural polysaccharides which is gaining extensive interest of researchers in the development of hydrogel is xanthan gum. Various modification techniques have been developed to enhance the solubility of xanthan gum. The employed methods for xanthan gum hydrogels formulation are: 1). Chemical Crosslinking with epichlorhydrine, glutaraldehyde, metabisulphate, citric acid and graft polymerization. 2). Physical crosslinking by polyelectrolytes complexation, ionotropic gelation and freeze thaw technique. Xanthan gum and xanthan gum derivatives hydrogel systems can be employed in explicit areas; thus providing us pharmaceutically highly acceptable delivery system for site specific and controlled release; of drugs and enzymes.

Background: Lipid peroxidation induced by drug can be considered as drug induced toxicity. The concept of antioxidant co-therapy may be the way of future formulation design with an aim of reducing drug induced toxicity. Objective: The current study was designed to evaluate the anti-peroxidative activity of quercetin and ascorbic acid on anti cancer drug (6-Mercaptopurine/Methotrexate) induced lipid peroxidation. Method: Study was carried out by Reverse Phase HPLC method for the measurement of free malondialdehyde (a relevant biomarker for lipid peroxidation estimation) in goat liver. After the preparation of standard curve for malondialdehyde estimation, a tissue homogenate of goat liver was prepared and divided in to six different groups and were treated with the anti- cancer drugs and antioxidants. Then after, 2 hours of incubation, the supernatant was collected, filtered and procured to inject in RP-HPLC using mobile phase 30 mM potassium di hydrogen phosphate and Methanol (65:35, v/v %), at pH of 4. Result: 6-Mercaptopurine/Methotrexate showed significant increase in malondialdehyde concentration (45.12% and 12.66 %) respectively as compared to control group. Wherever, concentration was significantly reduced in anticancer drugs in combination with antioxidants (41.74 %, -34.91 % and -26.96 %,-73.56 %). While, concentration of malondialdehyde (-75.01 %, 62.30 %) was reduced in antioxidant treated group in comparison to control and drug treated groups. Conclusion: It was revealed that quercetin and ascorbic acid have beneficial effect to suppress or decrease the drug induced changes in lipid profile of liver samples.

Background: Nanostructured hybrid antibiotics (NHAs) are a new class of substances with a high potential in the development of novel alternatives for antimicrobial treatments. This strategy is based on the building of synergy between biologically-active organic and inorganic substances. Objective: The aim of this study was to develop hydrogels based in cassava starch for controlled release systems with antibacterial and antibiofilm properties using nanostructured hybrid systems. Method: For that, hydrogels were synthesized from cassava starch and poly(acrylic acid) (PAA) by esterification reaction. Silver nanoparticles were synthesized by chemical reduction using NaBH4 as reducing agent and citrate as capping agent. Nanostructured hybrid systems were prepared from silver nanoparticles (AgNPs) and cysteamine (cysa) by ligand exchange reaction; these systems were characterized (Fourier transform infrared, dynamic light scattering, elemental analysis) and evaluated against Escherichia coli and Staphylococcus aureus using Tryptic Soy Broth as liquid phase. Conclusion: Hydrogels can be used as controlled-release systems of substance with antibacterial activity (AgNPs, cysa and AgNPs-cysa). Antibacterial effect against Escherichia coli and Staphylococcus aureus was seen to be relatively low at studied concentrations; however, the charge of antimicrobial activity can be controlled as a result of high water absorption capacity. Inhibition percent for hybrid systems (AgNPs-cysa) was seen to be most effective against Escherichia coli and very similar to the observed effect for AgNPs.

Background: Polyphenols are secondary metabolites of plants which are generally associated with the protection against ultraviolet radiation and aggression by pathogens. Epidemiological studies suggest that long term consumption of diets rich in plant polyphenols offer protection against different diseases with positive effects in the context of human health. Objective: The objective of this work was to develop biodegradable polymer hydrogels (HGs) based in sorbitol and citric acid for controlled release of bioactive substances from plants (specifically strictinin). Method: HGs were synthesized at two relation sorbitol:citric acid (1:1 and 1:2) and characterized by ATRFTIR. In addition, it was determined its water absorption capacity by tea bag method. Hydrolysis of strictinin was studied at different pH and release of strictinin was monitored by UV-vis. Antimicrobial activity of strictinin in solution and in the HGs was tested against E. coli and S. aureus. Results: HGs can be synthesized from sorbitol and citric acid by free-solvent synthesis. These HGs can be used for the release of strictinin at acid pH without changes in its chemical structure; at alkaline pH, hydrolysis processes affect its strictinin chemical structure. Diffusion of strictinin is slower in HG 1:1 than HG 1:2, being the released quantity by diffusion in both cases are the same. In addition, only 29.8 % of strictinin can be release by diffusion and, in consequence, the remaining strictinin must be released by other mechanism. Conclusion: Results evidence that E. coli and S. aureus are sensitive to low strictinin concentrations (2.43 mgL-1) released from HGs.

Objective: In this study, an attempt has been made to modify k-Carrageenan properties by grafting acrylamide chain and use to develop a pH sensitive hydrogel beads composed of grafted kcarrageenan and sodium alginate for the controlled delivery of diltiazem hydrochloride. Material: The hydrogel beads were prepared by the ionotropic gelation method using aluminium chloride (AlCl130;ƒ) as a cross-linking agent. The characterization of diltiazem HCl loaded beads was done by scanning electron microscopic, Fourier transform infrared spectroscopic, differential scanning calorimetry and X-ray powder diffraction analysis. Result: The surface morphology revealed that the prepared beads were spherical, having rough with microscopic cracks in the surface. The X-ray diffraction study indicates that the drug was dispersed molecularly in the polymer matrix and amorphous in nature in the bead. The beads were evaluated for bead size, drug entrapment efficiency, swelling ratio and in-vitro drug release study. The size of beads was in decreasing trend with increasing the AlCl3 concentration. The drug entrapment efficiency of the beads was decreased with the increase in AlCl3 concentration. The swelling of the beads decreased in both acidic and basic medium with increasing AlCl3 concentration. The drug release rate of beads was decreased when AlCl3 concentration increased. Conclusion: The preliminary investigation of the beads developed in this study showed a promising sustained release profile of the drug. Therefore, the cross-linked hydrogel beads are promising carriers for oral controlled release of water soluble drug diltiazem HCl.

Background: The aggregation of the amyloid-beta peptide (Aβ) in the brain is strongly associated with Alzheimer's disease (AD). However, the heterogeneous and transient nature of this process has prevented identification of the exact molecular form of Aβ responsible for the neurotoxicity observed in this disease. Therefore, characterizing Aβ aggregation is of utmost importance in the field of AD. Nuclear magnetic resonance spectroscopy (NMR) is a technique that holds great potential to achieve this goal. However, it requires the use of specific labels introduced through recombinant expression of Aβ. Objective: In this paper, we report on a straightforward expression and purification protocol to obtain [U-15N] and [U-2H,13C,15N] Aβ42. Method: Aβ42 is expressed fused to Small Ubiquitin-like Modifier (SUMO) protein, which prevents Aβ42 aggregation. Results: The solubilizing capacity of SUMO has allowed us to design a purification protocol involving immobilized metal affinity chromatography (IMAC), a desalting step, and two size exclusion chromatography (SEC) purifications. Conclusion: This approach, which does not require the use of costly and time-consuming reversed phase high performance liquid chromatography (RP-HPLC), offers a much straightforward strategy to those previously described to obtain [U-15N] Aβ42 and it is the first protocol through which to achieve [U-2H,13C,15N] Aβ42. The peptides obtained are of high purity and have the required isotope enrichment to support NMR-based structural studies.

Background and Objective: CsaA is a molecular chaperone known to prevent aggregation of preproteins and also involved in the post-translational translocation of the proteins across the cytoplasmic membrane after correct folding. CsaA is known to be present in prokaryotes but is absent in eukaryotes. Although bacterial CsaA has been studied to some extent, there are no reports yet of crystallographic studies of CsaA from any of the archaeal organisms. Method: In the present investigation, we report for the first time the cloning, expression, purification and crystallographic diffraction data collection on CsaA from Picrophilus torridus (PtCsaA), which is a thermoacidophilic archaeon. PtCsaA was cloned in pET28a(+) and expressed in E. coli BL21(DE3), purified using metal affinity and gel filtration chromatography. Results and Conclusion: Crystallization trials with purified PtCsaA protein resulted in crystals suitable for Xray diffraction analysis. The crystals belonged to the orthorhombic space group P212121 and diffracted to the resolution limit of about 1.70 Å. Structure solution is expected to proceed using molecular replacement methods. The comparison of the resulting model structure to its counterparts from bacteria is expected to throw light on the structural similarities and differences between the homologs found in the two prokaryotic domains.