Vishnu Agarwal

Biomedical applications of carboxymethyl chitosans

This review outlines the recent developments on carboxymethyl chitosan-based bio-medical applications. Carboxymethyl chitosan, a water soluble derivative of chitosan, with enhanced biological and physicochemical properties compared to chitosan, has emerged as a promising candidate for different biomedical applications. Introducing small chemical groups like carboxymethyl to the chitosan structure can drastically increase the solubility of chitosan at neutral and alkaline pH values without affecting their characteristic properties. Due to improved biocompatibility, high moisture retention ability more viscosity and enhanced antimicrobial property of carboxymethyl chitosan than chitosan makes it promising candidate for hydrogels and wound healing applications. The biodegradability and biocompatibility of carboxymethyl chitosan has significant interest with application as biomaterial for tissue engineering. Apart from this, the easy of carboxymethyl chitosan can be easily processed into nanoparticles so it has shown promise for drug delivery, bioimaging, biosensors and gene therapy applications. The contribution of carboxymethyl chitosan to green chemistry in the recent years has also been given in detail. This review will focus on preparative methods and physicochemical and biological properties of carboxymethyl chitosan with particular emphasis on biomedical and pharmaceutical applications of this derivative of chitosan.

The implications of recent advances in carboxymethyl chitosan based targeted drug delivery and tissue engineering applications

Over the last decade carboxymethyl chitosan (CMCS) has emerged as a promising biopolymer for the development of new drug delivery systems and improved scaffolds along with other tissue engineering devices for regenerative medicine that is currently one of the most rapidly growing fields in the life sciences. CMCS is amphiprotic ether, derived from chitosan, exhibiting enhanced aqueous solubility, excellent biocompatibility, controllable biodegradability, osteogenesis ability and numerous other outstanding physicochemical and biological properties. More strikingly, it can load hydrophobic drugs and displays strong bioactivity which highlight its suitability and extensive usage for preparing different drug delivery and tissue engineering formulations respectively. This review provides a comprehensive introduction to various types of CMCS based formulations for delivery of therapeutic agents and tissue regeneration and further describes their preparation procedures and applications in different tissues/organs. Detailed information of CMCS based nano/micro systems for targeted delivery of drugs with emphasis on cancer specific and organ specific drug delivery have been described. Further, we have discussed various CMCS based tissue engineering biomaterials along with their preparation procedures and applications in different tissues/organs. The article then, gives a brief account of therapy combining drug delivery and tissue engineering. Finally, identification of major challenges and opportunities for current and ongoing application of CMCS based systems in the field are summarised.

Effect of Cinnamon Oil on Quorum Sensing-Controlled Virulence Factors and Biofilm Formation in Pseudomonas aeruginosa

Quorum sensing (QS) is a system of stimuli and responses in bacterial cells governed by their population density, through which they regulate genes that control virulence factors and biofilm formation. Despite considerable research on QS and the discovery of new antibiotics, QS-controlled biofilm formation by microorganisms in clinical settings has remained a problem because of nascent drug resistance, which requires screening of diverse compounds for anti-QS activities. Cinnamon is a dietary phytochemical that is traditionally used to remedy digestive problems and assorted contagions, which suggests that cinnamon might contain chemicals that can hinder the QS process. To test this hypothesis, the anti-QS activity of cinnamon oil against P. aeruginosa was tested, measured by the inhibition of biofilm formation and other QS-associated phenomena, including virulence factors such as pyocyanin, rhamnolipid, protease, alginate production, and swarming activity. To this end, multiple microscopy analyses, including light, scanning electron and confocal microscopy, revealed the ability of cinnamon oil to inhibit P. aeruginosa PAO1 biofilms and their accompanying extracellular polymeric substances. This work is the first to demonstrate that cinnamon oil can influence various QS-based phenomena in P. aeruginosa PAO1, including biofilm formation.

Nanoparticle-based Drug Delivery Systems: Promising Approaches Against Infections

Despite the fact that many new drugs and technologies have been developed to combat the infectious diseases, these have continued to be global health challenges. The use of conventional antimicrobial agents against these infections is always associated with problems such as the development of multiple drug resistance and adverse side effects. In addition, the inefficient traditional drug delivery system results in inadequate therapeutic index, low bioavailability of drugs and many other limitations. In this regard, antimicrobial nanoparticles and nanosized drug delivery carriers have emerged as potent effective agents against the infections. Nanoparticles have unique properties owing to their ultra small and controllable size such as high surface area, enhanced reactivity, and functionalizable structure. This review focused on different classes of antimicrobial nanoparticles, including metal, metal oxide and others along with their mechanism of action and their potential use against the infections. The review also focused on the development of nanoparticle systems for antimicrobial drug delivery and use of these systems for delivery of various antimicrobial agents, giving an overview about modern nanoparticle based therapeutic strategies against the infections.

In situ grafted nanostructured ZnO/carboxymethyl cellulose nanocomposites for efficient delivery of curcumin to cancer

In this present manuscript, zinc oxide (ZnO) nanoparticles embedded carboxymethyl cellulose (CMC) bionanocomposite were prepared by in situ grafting and the hydrophobic anticancer drug curcumin (Cur) was loaded into it. Structural, morphological, and physiochemical behavior of prepared curcumin-loaded CMC/ZnO nanocomposites (NCs) were characterized by FTIR, XRD, SEM, TEM, TGA, and DTA. The drug entrapment efficiency was evaluated and the in vitro efficacy as anticancer drug delivery vehicle was analyzed. The potential toxicity of curcumin-loaded ZnO/CMC NCs (Cur/ZnO/CMC NCs) was studied by using L929 and MA104 cell lines via MTT assay. The cellular uptake study of Cur/ZnO/CMC NCs by normal (L929) and cancer (MA104) cells carried out by using ethanol extraction and by FACS analysis has been reported. The results of this investigation demonstrate that the nanomatrix synthesized can effectively deliver the anticancer drug curcumin, and hence appears to be a promising nanoformulation for anticancer therapy and other biomedical applications.

Structure based virtual screening for identification of potential quorum sensing inhibitors against LasR master regulator in Pseudomonas aeruginosa

Inter and intracellular communication in bacteria, which is known as quorum sensing (QS), is mediated by small diffusible signaling molecules known as autoinducers. QS regulates various virulence factors responsible for pathogenesis. Increasing resistance of microorganisms against traditional antibiotics has turned the focus towards the QS as it exerts less selective pressure preventing development of resistance among microorganisms. LasR, a transcription factor that controls QS in Pseudomonas aeruginosa, is an attractive therapeutic target for inhibitors. This study aimed to screen natural compounds as potential inhibitors of LasR. About 2603 compounds from ZINC database were virtually screened against the structure of LasR. Then after qualifying compounds were filtered on the parameters of Lipinskis rule and ADME. Six novel potential QS inhibiting compounds were selected on the basis of binding energy. Structures of LasR-ligand complexes were analysed to have insight of binding between inhibitors and target. It is pertinent to mention here that all the molecules are structurally different from 3-oxo-C12HSL,a native autoinducer of LasR, that play key role in formation of LasR dimer which is an active form of the protein to facilitate QS.

Exploring the impact of parthenolide as anti-quorum sensing and anti-biofilm agent against Pseudomonas aeruginosa

Aims: Pseudomonas aeruginosa is a well‐known pathogen responsible for various infections due to its capability to develop biofilm and various virulent phenotypes that are regulated by quorum sensing. Pathogenesis of the bacteria may be halted by interfering with the signaling molecules and the quorum sensing receptors. Therefore, the present study explores the potential of parthenolide, a sesquiterpene lactone of feverfew plant, as a promising candidate against P. aeruginosa PAO1 associated virulence factors and biofilm. Main methods: Effect of parthenolide on virulence and biofilm formation of P. aeruginosa was studied using standard protocols. Mechanism of action was studied using Real‐time PCR as well as molecular docking studies. Key findings: Significant decrease in virulence factors and biofilm formation was observed when treated with the sub‐MIC concentration (1 mM) of parthenolide. Gene expression studies showed the down‐regulation of autoinducer synthase (lasI, rhlI) as well as their receptors (lasR and rhlR) with remarked repression of lasR by 57% compared to the control. Biofilm‐associated fluorescent microscopic studies after staining with FITC‐ConA and propidium iodide showed reduced extracellular polymeric substance (EPS) production and killing of bacterial cells after treatment with parthenolide. Significance: The study is important as it reports for the first time the potential of parthenolide as an anti‐quorum and anti‐biofilm agent. This study will be helpful in designing of new quorum sensing inhibitors that help in the eradication of infections and can be given in combination with the antibiotics.

Pseudomonas aeruginosa quorum sensing molecule N-3-oxo-dodecanoyl-l-homoserine lactone activates human platelets through intracellular calcium-mediated ROS generation

Pseudomonas aeruginosa, an opportunistic pathogen release N-3-oxo-dodecanoyl-l-homoserine lactone (3-oxo-C12HSL) and N-butyryl-l-homoserine lactone (C4-HSL) quorum sensing (QS) molecules to regulate various virulence factors responsible for infection in the host. 3-oxo-C12 HSL not only regulates the bacterial gene expression but also modulates the host cell system. Thus, it is pertinent to evaluate the effect of these QS molecules on blood platelets which is responsible for the maintenance of hemostasis and thrombus formation. Here, in the present study, we showed that 3-oxo-C12 HSL activates platelets in a dose-dependent manner and induces intracellular calcium-mediated reactive oxygen species (ROS) release, whereas no such effect was observed with C4-HSL. 3-oxo-C12 HSL stimulated ROS release was mediated by NADPH oxidase. Results confirmed the involvement of phospholipase C (PLC) and IP3 receptor behind intracellular calcium-mediated ROS generation. The impact of 3-oxo-C12 HSL on platelet activation suggests that it could interfere and alter the normal function of platelet in individuals infected with P. aeruginosa.