A Transparent, Tough and Self-Healable Biopolymeric Composites Hydrogel for Open Wound Management.

Modern healthcare engineering requires a wound dressing solution supported by materials with outstanding features such as high biological compatibility, strong mechanical strength, and higher transparency with effective antibacterial properties. Here, we present a unique hydrogel technology consisting of two negatively charged biopolymers and a positively charged synthetic polymer. The interaction between charged polymers through hydrogen bonds has been created, which are revealed in the simulation by density functional theory and Fourier transform infrared spectra of individual polymers and the hydrogel film. The transparent hydrogel film dressings showed excellent stretchability, a higher water swelling ratio (60%), and strong mechanical strength (∼100 MPa) with self-healing abilities (85-90%). The fabricated hydrogel film showed stable blood clots (within 119 ± 15 s) with rapid hemostasis (<2%) properties and effective antibacterial studies against E. coli and S. aureus bacterial strains. In addition, the obtained hydrogel film also showed excellent cell viability on mouse fibroblast cells. With their enormous amenability to modification, these hydrogel films may serve as promising biomaterials for wound dressing applications.

Computational insight of antioxidant and doxorubicin combination for effective cancer therapy.

Doxorubicin (DOX) is the most effective antineoplastic agent, destroys cancer cells by interrupting cellular function. However, the serious side effects on the heart limits its utility. To curb these unwanted side effects, nutritionist recommend antioxidants use along with DOX while chemotherapy. But it was not supported by various oncologists as it can alter the toxicity of DOX towards cancer cells. Therefore, here we explored the in silico pharmacokinetics and combination effect of DOX and antioxidants on topoisomerases-II (Top-II) and cyclophilin D (Cyp-D) therapeutic targets involved in cancer proliferation and post-myocardial infarction, respectively. The molecular docking study was conducted on target proteins and DOX including most prescribed antioxidants (melatonin, N-acetylcysteine (NAC), glutathione (GSH), ß-carotene and vitamin C). GSH showed effective binding potential for Top-II and Cyp-D active sites, but other considered antioxidants possess low binding affinity. The highest docked conformations were subjected to molecular dynamics (MD) simulations to understand conformer stability of DOX and GSH with Cyp-D and Top-II for 100 ns. The results revealed that ligands pose at Top-II active sites where DOX showed strong binding affinity to DNA binding pocket and GSH to a buried site. The computational data summarised and proposed the GSH and DOX combination as antagonist effects on Top-II. Conversely, the binding compactness of GSH improved due to surface fit at the active pocket of Cyp-D and completely blocking DOX binding affinity, suppress adverse reactions of post-myocardial infarction.Communicated by Ramaswamy H. Sarma.

Structural Distortion of ß-Cyclodextrin Plays a Key Role in the pH-dependent Host-Guest Chemistry with Doxorubicin, Evident by the Electrochemical and Molecular Dynamics Approach.

ß-Cyclodextrin (ß-CD) is the potential drug carrier to deliver antitumor drugs like doxorubicin (DOX). However, the mechanism for the inclusion complex formation is still unclear and needs to be explored. This study investigated the effect of pH on the inclusion of DOX into thiolated ß-CD (ß-CD-SH) by electrochemical and molecular dynamics (MD) simulation. The electrochemical study shows a clear difference at different pH values. The redox peak due to the DOX is strongly influenced by pH. At neutral pH, the peak intensity decreases with time, while slight variation is observed at acidic and basic pH, depicting the association of DOX to the ß-CD-SH cavity at neutral pH. Also, due to the association, the charge transfer resistance variation increased with time at neutral pH and decreased at basic and acidic pH. The electrochemical study was further supported by MD simulation, suggesting that the cyclodextrin (CD) ring gets slightly elongated due to the flipping of glucose units, specifically at neutral pH leading to a strong association. Also, another significant result observed that the DOX forms an inclusion complex with ß-CD-SH in quinol conformation, not in quinone. Briefly, the study provides the necessary molecular binding information for designing an effective ß-CD-based targeted drug delivery system.

Glutathione conjugated superparamagnetic Fe3O4-Au core shell nanoparticles for pH controlled release of DOX.

Glutathione (GSH) coated gold­iron oxide core shell nanoparticles (GS-Au-Fe3O4) were prepared by coating glutathione shell on nanoparticles to reduce the dose dependent behaviour of anticancer drug, doxorubicin (DOX). The resultant nanoparticles were characterized using XPS, FTIR, HR-TEM with STEM profile to analyze the GSH shell over the surface. The GS-Au-Fe3O4 nanoparticles were loaded with DOX and maximum drug entrapment capacity of 54% was observed in 48 h. In-vitro drug release were evaluated using UV-vis and Fluorescence spectroscopy. The results show that drug release is facilitated under acidic conditions as well as by extracellular glutathione spiking. Cytotoxicity and cellular uptake was studied on HeLa cells where GS-Au-Fe3O4 nanoparticles lead to significantly higher uptake of DOX as compared to free drug. The use of glutathione conjugation thus act as an efficient drug delivery vehicle which requires significantly low concentration of GS-Au-Fe3O4 nanoparticles for DOX release besides triggering drug release by using redox active GSH.

Electrochemical impedance spectroscopy reveals a new mechanism based on competitive binding between Tris and protein on a conductive biomimetic polydopamine surface.

A novel mechanism was developed to study the interaction of mussel inspired polydopamine surfaces with bovine serum albumin using cyclic voltammetry and electrochemical impedance spectroscopy supplemented with XPS, IR spectroscopy, UV spectroscopy and atomic force microscopy. The polydopamine surfaces reveal different mechanisms that give a new insight into understanding the interaction with BSA under the variable conditions used for PDA preparation and BSA adsorption. The study provides an in-depth analysis of the orientations and interactions of BSA with polydopamine surfaces. The protein interaction behavior changed significantly in different environments including different pH values and concentrations of buffer and it revealed a competitive binding mechanism of protein binding. The study provides an outlook for studying the interaction of protein foulants with PDA, which should be carried out in nucleophilic buffers, while the covalent binding or immobilization of biomolecules to PDA surfaces should be carried out in non-nucleophilic buffer for higher efficiency.