Baskaran Purushothaman

The Application of Bactericidal Silver Nanoparticles in Wound Treatment

Even with the prevalence of wounds, the medical technology for efficiently managing skin damage is still primitive. The disruption of any of the numerous healing processes can lead to problems in the time-sensitive healing actions of the dermal and epidermal layers. Bacterial infection is one of the major obstacles to proper wound healing as it poses a danger of causing long-term negative effects. Keeping the wound free of bacteria is imperative to the proper and hasty repair of dermal wounds. Silver has been widely used to treat wounds for its bactericidal properties. Although the mechanism of silvers antibacterial action is not fully understood, it exhibits a significant antimicrobial efficacy against a wide spectrum of bacterial species. A number of different approaches to the mechanism are reported and presented in this review. Silver nanoparticles (AgNPs) have been reported to exhibit enhanced antibacterial activity due to their increased surface-area-to-volume ratio. AgNPs are capable of various modifications, significantly broadening the therapeutic properties of the material as a result. This review explores the different aspects of silver and silver nanoparticles, and their antibacterial properties, which can be applied in the field of wound treatments.

Investigating the versatility of multifunctional silver nanoparticles: preparation and inspection of their potential as wound treatment agents

Silver nanoparticles (AgNPs) are capable of inhibiting the growth of a broad spectrum of bacterial species. The minute size of the nanoparticulates enhances their biocidal activity and is thus widely utilized as antibacterial agents. The most recently researched and recognized antibacterial and wound-healing properties of published AgNPs were investigated in this article. The following parameters of the AgNPs affecting their properties and potency were explored: particle size, shape, and type of ligand or stabilizing agent. Research regarding the antibacterial activity enhancement of high-valent silver nanoparticles compared to those of the lower valent forms were summarized and analyzed. Nanocrystalline silver is capable of binding to components that may enhance their preparation and antibacterial properties. By forming complexes with ligands that exhibit desired properties, silver nanoparticles can be synthesized to exhibit those desired properties without compromising their performance. This review will provide a detailed discussion regarding the parameter-dependent bactericidal properties of silver nanoparticles and nanocomposite silver complexes as potent multifunctional wound-healing agents.Graphical Abstract

Insulin-mimetic and anti-inflammatory potential of a vanadyl-Schiff base complex for its application against diabetes

Insulin signalling causes the translocation of glucose transporter 4 (GLUT4) to the plasma membrane to facilitate cellular glucose uptake. Numerous observations indicate that the prime cause of type 2 diabetes mellitus (T2DM) is inflammation, the occurrence of which increases in obese individuals. Inflammatory mediators induce an insulin-resistance (IR) state where impaired insulin signalling fails to promote the glucose transporters for intracellular uptake of glucose. Hence compounds, which possess insulin-mimetic and anti-inflammatory potentials, may be effective in the treatment of obesity-induced IR during T2DM. Previous studies showed that vanadium oxo complexes possess insulin-mimetic activities whereas the tryptamine moiety offers anti-inflammatory potential. Hence a vanadyl-Schiff base complex (VOTP) consisting of the tryptamine moiety was synthesized by condensation of pyridoxal hydrochloride and tryptamine and its subsequent complexation with VOSO4. HEK-293 cells, expressing a GLUT4-myc-GFP fusion protein, were treated with VOTP and GLUT4 translocation was quantified by total internal reflection fluorescence (TIRF) microscopy. Results indicated that VOTP could efficiently act as an insulin-mimetic substance. A high-content cell based assay using quantum dot–antibody conjugates showed that VOTP restored insulin signaling during IR by the inactivation of c-Jun N-terminal kinase-1 (JNK-1) and subsequent phosphorylation and activation of the tyrosine moiety of insulin receptor substrate (IRS). Also, high levels of phosphorylated Forkhead box O1 (FOXO) indicated low levels of gluconeogenesis. Hence VOTP has insulin-mimetic and anti-inflammatory potentials. Moreover, VOTP is highly effective at nanomolar treatment ranges, thus evades the toxicity issues. Collectively, these findings encourage us for future use of this compound as a potential anti-diabetic agent.

Design, synthesis, and biological evaluation of novel catecholopyrimidine based PDE4 inhibitor for the treatment of atopic dermatitis

Selective inhibition of phosphodiesterase (PDE) 4B favorably suppresses the synthesis of inflammatory cytokines and subsequently arrest the development of atopic dermatitis via modulating the intracellular cAMP levels. Considering the side effects of corticosteroids, selective PDE4 inhibition could constitute an effective alternative therapy for the treatment of atopic dermatitis (AD). In this study, a series of novel catechol based compounds bearing pyrimidine as the core have been synthesized and screened for the PDE4 inhibitory properties. The PDE4 selectivity of the active compounds over other PDEs has been investigated. Compound 23 bearing pyrimidine core functionalized with catechol, pyridine and trifluoromethyl groups can effectively inhibit the PDE4B with IC50 value in nanomolar range (IC50 = 15 ± 0.4 nM). Compound 23 exhibited seven fold higher selectivity towards PDE4B over PDE4D. Molecular Docking study confirmed its stronger affinity towards catalytic domain of PDE4B. In-vivo analysis confirmed that compound 23 effectively alleviated the symptoms of atopic dermatitis in DNCB-treated Balb/c mice by suppressing the synthesis of inflammatory mediators such as TNF-α, and Ig-E. Taken together, this study suggested that compound 23 could be an effective PDE4 inhibitor for the potential treatment of AD.

Preparation of high-valence bifunctional silver nanoparticles for wound-healing applications

Abstract The antibacterial properties of silver nanoparticles (AgNPs) depends on the valence form of the silver ion. It is well established that the higher valent silver ion showed better antibacterial activity than the lower valent silver ion. The higher valent, monodisperse nanoparticles of silver chlorhexidine and silver-pyridoxine complex were synthesized by reverse microemulsion technique. The antibacterial activity of nanoparticles was tested against different gram-positive and gram-negative pathogenic bacteria accountable for the infection of burn wounds. A kinase pathway study established that silver-pyridoxine nanoparticles encouraged the proliferation and migration of keratinocyte and fibroblast cells. In this chapter, we address bimodal therapeutic AgNPs that have direct wound-healing and antibacterial properties. The wound healing activity of nanoparticles was verified by in vitro assays and also in diabetic mice. The fast wound-healing that takes place on skin wounds of diabetic mice demonstrates the utility of bimodal therapeutic AgNPs as a next-generation topical agent.

A Novel Catecholopyrimidine Based Small Molecule PDE4B Inhibitor Suppresses Inflammatory Cytokines in Atopic Mice

Degradation of cyclic adenosine mono phosphate (cAMP) by phosphodiesterase-4B (PDE-4B) in the inflammatory cells leads to elevated expression of inflammatory cytokines in inflammatory cells. Suppression of cytokines has proved to be beneficial in the treatment of atopic dermatitis (AD). Henceforth, application of PDE4B specific inhibitor to minimize the degradation of cAMP can yield better results in the treatment of AD. PDE4B specific inhibitor with a limited side effect is highly warranted. Herein, we synthesized a novel PDE4 inhibitor, compound 2 comprising catecholopyrimidine core functionalized with trifluoromethyl (-CF3) group. PDE4B inhibitory potential and specificity of novel compounds were evaluated by PDE inhibitor assay. In vivo efficacy of the compounds was analyzed using DNCB-induced NC/Nga mice. IgE, CD4+ T-helper cell infiltration, and cytokine profiles were analyzed by ELISA and immunohistochemistry techniques. Toluidine blue staining was performed for mast cell count. PDE4 inhibitor assay confirmed that compound 2 specifically inhibits PDE4B. In vivo analysis with DNCB-induced NC/Nga mice confirmed that compound 2 suppressed the levels of pro-inflammatory cytokines such as TNF-α, IL-4, IL-5, and IL-17. Furthermore, compound 2 significantly reduced the infiltrative CD4+ T-helper cells, mast cells and IgE levels in atopic tissue. The in vitro and in vivo data suggested that compound 2 specifically inhibit the PDE4B and the symptoms of the AD in atopic mice. Compound 2 might constitute a good candidate molecule for the treatment of AD.