Browsing by Author "Akhil, V"

Now showing 1 - 6 of 6
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    Cascade of immune mechanism and consequences of inflammatory disorders
    (Phytomedicine, 2021-10) Megha, KB; Joseph, X; Akhil, V; Mohanan, PV
    Inflammatory responses arise as an outcome of tissues or organs exposure towards harmful stimuli like injury, toxic chemicals or pathogenic microorganism. It is a complex cascade of immune mechanism to overcome from tissue injury and to initiate the healing process by recruiting various immune cells, chemical mediators such as the vasoactive peptides and amines, pro-inflammatory cytokines, eicosanoids and acute-phase proteins to prevent tissue damage and ultimately complete restoration of the tissue function. The cytokines exhibits a central function in communication between the cells, inflammatory response initiation, amplification and their regulation. This review covers the importance of inflammatory responses; the significance of cytokines in inflammation and numerous inflammatory disorders/ailments due to the abrupt expression of cytokines and the hyper-inflammatory response or cytokine storm associated with poor prognosis in COVID-19 pandemic. Also highlighting the importance of naturally derived anti-inflammatory metabolites to overcome the side-effects of currently prevailing anti-inflammatory drugs.
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    Cellular and sub-chronic toxicity of hydroxyapatite porous beads loaded with antibiotic in rabbits, indented for chronic osteomyelitis
    (International Journal of Pharmaceutics, 2022-02) Vandana, U; Akhil, V; Suresh Babu, S; Francis, B; Sabareeswaran, A; Varma, HK; Mohanan, PV
    Bioceramics have emerged as a hopeful remedy for site-specific drug delivery in orthopaedic complications, especially in chronic osteomyelitis. The bioresorbable nature of bioceramic materials shaped them into a versatile class of local antibiotic delivery systems in the treatment of chronic osteomyelitis. Hydroxyapatite (HA) based bioceramics with natural bone mimicking chemical composition are of particular interest due to their excellent biocompatibility, better osteoconductive and osteointegrative properties. Although HA has been widely recognized as an efficient tool for local delivery of antibiotics, information regarding its subchronic systemic toxicity have not been explored yet. Moreover, a detailed investigation of in vivo subchronic systemic toxicity of HA is critical for understanding its biocompatibility and futuristic clinical applications of these materials as novel therapeutic system in its long haul. Evaluation of biocompatibility and sub-chronic systemic toxicity are significant determinants in ensuring biomedical device’s long-term functionality and success. Sub-chronic systemic toxicity allows assessing the potential adverse effects caused by leachable and nanosized wear particles from the device materials under permissible human exposure to the distant organs that are not in direct contact with the devices. In this context, the present study evaluates the sub-chronic systemic toxicity of in-house developed Hydroxyapatite porous beads (HAPB), gentamicin-loaded HAPB (HAPB + G) and vancomycin- loaded HAPB (HAPB + V) through 4 and 26-week muscle implantation in New Zealand white rabbits, as per ISO 10993–6 and ISO 10993–11. Analysis of cellular responses of HAPB towards Human Osteosarcoma (HOS) cell line through MTT assay, direct contact cytotoxicity, live/dead assay based on Imaging Flow Cytometry (IFC) showed its non-cytotoxic behaviour. Histopathological analysis of muscle tissue, organs like heart, lungs, liver, kidney, spleen, adrenals, intestine, testes, ovaries, and uterus did not reveal any abnormal biological responses. Our study concludes that the HAPB, gentamicin-loaded HAPB (HAPB + G) and vancomycin-loaded HAPB (HAPB + V) are biocompatible and did not induce sub-chronic systemic toxicity and hence satisfies the criteria for regulatory approval of HAs as a plausible candidate for
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    L-Cysteine capped zinc oxide nanoparticles induced cellular response on adenocarcinomic human alveolar basal epithelial cells using a conventional and organ-on-a-chip approach
    (Colloids and Surfaces B: Biointerfaces, 2022-03) Arathi, A; Joseph, X; Akhil, V; Mohanan, PV
    Zinc oxide nanoparticles (ZnO NPs) are among the well-characterized nanomaterials with multifaceted biomedical applications, including biomedical imaging, drug delivery, and pharmaceutical preparations. The high surface charge of ZnO NPs leads to the agglomeration of the particles. Therefore, surface coating with a suitable ligand can increase colloidal stability. In this present study, in-vitro responses of ZnO NPs capped with a sulfur-containing amino acid, L-cysteine (Cys-ZnO NPs), on A549 cells was investigated. Fourier Transform Infrared Spectroscopy (FTIR) studies were carried out to confirm the capping of ZnO NPs with L-cysteine. Cytotoxic studies using A549 cells demonstrated reduced cytotoxicity in comparison with already reported pristine Zinc Oxide nanoparticles. The cellular uptake is confirmed by fluorescent cytometry. However, a higher concentration (160 µg/mL) of Cys-ZnO NPs led to apoptotic cell death marked by nuclear condensation, mitochondrial membrane depolarization, actin filament condensation, lysosomal damage LDH leakage, intracellular ROS production, blebbing, upregulation of Bax and downregulation of Bcl-2 gene expression. Cys-ZnO NPs treatment was also carried out in cells cultured in a microfluidic lung-on-a-chip device under a physiologically relevant flow rate. The study concluded that the microfluidic-based lung-on-a-chip culture resulted in reduced cell death compared to the conventional condition.
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    Microfluidic synthesis of gelatin nanoparticles conjugated with nitrogen-doped carbon dots and associated cellular response on A549 cells
    (Chemico-Biological Interactions, 2022-01) Joseph, X; Akhil, V; Arathi, A; Mohanan, PV
    Gelatin nanoparticles are a versatile class of nanoparticles with wide applications, especially in drug delivery and gene delivery. The inherent biocompatible nature of gelatin and various functional groups can improve the cellular interactions and enhance the efficacy of different drug formulations. Microfluidic hydrodynamic flow-focusing techniques can be used for the synthesis of gelatin nanoparticles. The present work syntheses nitrogen-doped carbon dots conjugated with gelatin nanoparticles (NQD-GNPs) using a microfluidic approach and associated cellular response through various assays. MTT, neutral red uptake, and Calcein AM/Propidium iodide (PI) assays independently proved the biocompatible nature of NQD-GNPs. The NQD-GNPs treatment demonstrated a slight increase in reactive nitrogen species generation and lactate dehydrogenase release. However, it does not alter the mitochondrial membrane potential or lysosomal stability. The cellular uptake of NQD-GNP depends on the concentration and does not affect the apoptotic pathway of the cells. Most of the cells remained viable even after treatment with high concentrations of NQD-GNPs.
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    Nanobiomaterials in support of drug delivery related issues
    (Materials Science & Engineering B, 2022-05) Joseph, X; Akhil, V; Arathi, A; Mohanan, PV
    Nanobiomaterials have been widely accepted as potential drug delivery agents over the past decade. A wide variety of materials have been utilized as drug delivery carriers for various diseases like Cancer, Alzheimer's etc. Being the leading cause of death worldwide, effective drug delivery to cancer cells by using nanomaterials has become the most fascinating and dynamic regions of research. The decreased size of these materials increased permeability through physiological barriers, and increased cell to cell interactions are the properties that are highly suitable for drug delivery applications. Biocompatibility and biodegradability are added advantages of using nano biomaterials as drug delivery systems. However, to transfer the nanobiomaterials for advanced clinical applications, a detailed study should be established considering the interactions of these nanobiomaterials with the physiological environment. Moreover, the need for extensive toxicity studies will open up a new window for the effective translation of these materials into clinical drug delivery carriers. The integration of nanomedicine and drug delivery system framework is unquestionably the pattern that will stay in the field of innovative work for quite a long time. Herein, we highlight the challenges of nanobiomaterials related to drug delivery and the possible strategies utilized to overcome the drug delivery-related issues.
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    The Response of Hydroxychloroquine for Covid-19
    (Pharmacology and Toxicology., 2021-07) Joseph, X; Akhil, V; Megha, KB; Mohanan, PV