Browsing by Author "Radhakumary, C"

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    Calcium ion modulates protein release from chitosan-hyaluronic acid poly electrolyte gel
    (Poly. Eng. Sci., 2015-05) Krishna, AS; Radhakumary, C; Sreenivasan, K
    Polyelectrolyte complex (PEC) of chitosan (CH) and hyaluronic acid (HA) are widely used for skin, cartilage, and bone tissue engineering. However, no reports are seen on their response at high ionic media, like increased Ca21 where they are likely to be exposed in the form of bone constructs and the influence of these ions on modulating the release of incorporated entities such as drugs and growth factors. Here, we prepared freeze dried scaffolds of PEC of CH and HA (CH-HA) and characterized them by FTIR, TGA, SEM, and ESEM. FITC conjugated BSA, designated as FA, was incorporated into the PEC to study the release properties in response to Ca21. The swellability of CH-HA and the extent of drug release from the matrix, FA loaded CH-HA was studied in deionised water and aqueous Na1 and Ca21 solutions. Swelling and drug release were high for the matrix in aqueous Ca21 whereas it was remarkably low in water and Na1. Drug released was found to increase with concentrations of Ca21 (0.02–1.0M) indicating that CH-HA is a promising matrix for Ca21 responsive delivery of agents to accelerate healing of bone cracks, which is known to release high amount of Ca21.
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    Carbon dot based non enzymatic approach for the detection and estimation of glucose in blood serum
    (MATERIALS RESEARCH EXPRESS, 2016) Krishna, AS; Nair, PA; Radhakumary, C; Sreenivasan, K
    In this study we generated a simple, reliable and selective approach based on carbon dots (CDs) and 4-cyanophenylboronic acid (CPBA) for blood glucose sensing. The methodology relies on the quenching of the emission of CDs by CPBA followed by its recovery by glucose. The system consisting of CDs and CPBA was characterised by Fourier transform infra red spectrum, transmissions electron microscopic, dynamic light scattering instrument, UV-visible and fluorescence techniques. The response of the probe, CD-BA in presence of different concentrations of glucose was assessed. Linear range was obtained for glucose concentrations ranging from 1 to 30 mM. Interferences by other saccharides and various biomolecules coexisting in blood serum were negligible. The chemo sensor thus developed has been successfully used for the estimation of glucose in human blood serum. The system being sensitive, efficient and easy to perform is a promising platform for blood glucose sensing.
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    Chitosan-Comb-graft-Polyethylene Glycol Monomethacrylate-Synthesis, Characterization, and Evaluation as a Biomaterial for Hemodialysis Applications
    (JOURNAL OF APPLIED POLYMER SCIENCE, 2009) Radhakumary, C; Nair, PD; Nair, CPR; Mathew, S
    Chitosan was reacted with "Polyethylene glycol monomethacrylate" (PEGm) using a redox initiation method. Different compositions were prepared by varying the relative amount of PEGm in the feed. A maximum of 88% yield with 320% grafting could be achieved. The graft copolymerization was confirmed by FTIR, thermal, and XRD studies. Higher graft % could be achieved as the monomer used is a macro monomer of PEG and the resultant graft is a comb-like polymer. Grafting with PEGm did not affect the thermal stability of chitosan film significantly, however, it resulted in a marginal increase in the tensile strength of the films in the dry state. The products showed much improved swelling at pH 7.4 and pH 1.98 compared to the virgin chitosan. The preliminary biocompatibility evaluation showed that the materials are blood compatible and non-cytotoxic. Though the permeability to low molecular weight solutes like creatinine and glucose was equal to or better than commercial cellulose membranes, the copolymer films expressed comparatively less permeability to these solutes initially, due to the crystalline domains of PEO grafts that impede the transport. On exposure in the medium, this effect is nullified culminating in better permeability. The crystallization of PEG grafts was very helpful in preventing the permeation of the high molecular weight solute albumin, the leakage of which above a certain limit is dangerous to the patient. (C) 2009 Wiley Periodicals, Inc. J Appl Polym Sci 114: 2873-2886, 2009
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    Chitosan-graft-poly(vinyl acetate) for hemodialysis applications
    (JOURNAL OF APPLIED POLYMER SCIENCE, 2012) Radhakumary, C; Nair, PD; Nair, CPR; Mathew, S
    Chitosan was graft copolymerized with vinyl acetate using ceric ammonium nitrate as the initiator. The chitosan-g-poly(vinyl acetate) (chitosan-g-PVAc) membranes were found to be blood compatible, noncytotoxic, and biodegradable. The physicochemical characterization of the membranes revealed that the membranes possess the synergistic effect of the natural-synthetic hybrids of chitosan and PVAc with excellent mechanical stability and tunable hydrophilic/hydrophobic characteristics. The permeation characteristics of chitosan-g-PVAc membranes for four different solutes creatinine, urea, glucose, and albumin was studied in vitro at 37 degrees C for assessment of the suitability of them as hemodialysis membranes. The studies showed that the membranes exhibit higher permeability to creatinine, urea, and glucose compared with the commercial cellulose membrane and are impermeable to the essential nutrient albumin. Hence, the need for the development of biocompatible, mechanically strong dialysis membranes could be addressed with the modification of chitosan through grafting with PVAc. Potential applications like artificial kidney, artificial pancreas, and so forth, are envisaged from these membranes. (c) 2012 Wiley Periodicals, Inc. J Appl Polym Sci, 2012
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    Detection and imaging of fatty plaques in blood vessels using functionalized carbon dots
    (ANALYTICAL METHODS, 2015) Krishna, AS; Radhakumary, C; Sreenivasan, K
    The risk of developing atherosclerosis is proportional to the blood cholesterol level which in turn eventually leads to heart attack. Since a large number of asymptomatic young people have evidence of atherosclerosis, it is highly necessary to diagnose it at the earliest. This communication depicts a simple method to visualize cholesterol deposits using digitonin (DG) conjugated carbon dots (CDs). Physico-chemical characterization and preliminary blood compatibility evaluation of the functionalized CDs (CDDG) were successfully carried out. It is found that the probes could selectively bind cholesterol as evident from their ability to image cholesterol doped polymer films and tissues with heavy fatty plaques suspended in blood serum. An early visualization of cholesterol-rich plaques using fluorescent nanoprobes reported here may aid in the diagnosis of atherosclerosis and it seems that our finding may catalyze further developments in this imperative domain. The data that emerged from the study also indicate that the novel probe can be used for the selective detection of cholesterol in solution.
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    Drug loaded thermoresponsive and cytocompatible chitosan based hydrogel as a potential wound dressing
    (CARBOHYDRATE POLYMERS, 2011) Radhakumary, C; Antonty, M; Sreenivasan, K
    There is a demand for a wound dressing which can be removed from the application site easily without causing any pain or discomfort A material removable by manipulating the temperature (e g moisten with ice cold water) from that point of view seems to have considerable potential Here we report a new formulation consisting of thiolated chitosan with poly(N-isopropyl acrylamide) loaded with ciprofloxacin The thermoresponsive material was cytocompatible and was found to modulate the release of the incorporated ciprofloxacin in a sustained fashion reflecting its suitability to protect a wound for a prolonged period The film exhibited adequate mechanical strength and was removable from a substrate (e g tissue culture plate) by lowering the temperature The combination of thiolated chitosan with poly(N-isopropyl acrylamide) and ciprofloxacin showed antibacterial properties to the virulent bacteria E colt supporting its potential as a wound dressing (C) 2010 Elsevier Ltd All rights reserved
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    Endomyocardial fibrosis is associated with selective deposition of type I collagen.
    (Indian heart journal, 2001)
    BACKGROUND: Endomyocardial fibrosis is a distinct form of heart disease leading to restrictive ventricular filling and cardiac failure. The disease is characterized by a marked thickening of the endocardium due to the deposition of dense fibrous tissue composed of wavy bundles of collagen. Changes in collagen composition and an abnormal increase in its concentration result in a stiffer myocardium and ventricular diastolic dysfunction. The nature of cardiac collagens and the relative proportions of collagen types in endomyocardial fibrosis have not been documented in the literature.METHODS AND RESULTS: This study analyzed collagen composition in the cardiac tissues of 13 patients with endomyocardial fibrosis and 6 individuals who were the victims of traffic accidents or suicidal deaths and did not have any heart disease. We estimated the relative proportions of types I and III collagen after pepsin digestion of the tissue and separation of the emerging peptides by sodium dodecyl sulfate polyacrylamide gel electrophoresis. The mean type I:III collagen ratio was 0.51+/-0.06 in normal individuals, and 0.93+/-0.43 in patients with endomyocardial fibrosis (p<0.05). The alteration in the type I:III collagen ratio was due to a disproportionate increase in type I collagen.CONCLUSIONS: The results indicate that a selective increase in type I collagen may contribute to the impaired diastolic distension of the ventricles in patients with endomyocardial fibrosis.
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    Functionalized carbon dots enable simultaneous bone crack detection and drug deposition
    (J. Mater. Chem B., 2015-01) Shanthikrishna; Radhakumary, C; Antony, M; Sreenivasan, K
    Recently, carbon dots (CDs) have become one of the most sought nanomaterials for biological applications owing to their excellent fluorescence, chemical inertness and biocompatibility. This article depicts the generation of a fluorescent nano probe using CDs for viewing bone cracks and simultaneous drug delivery to the cracked or infected sites. Water soluble polyethylene glycol diamine capped CDs were conjugated with glutamic acid (GA), a calcium targeting ligand, and ciprofloxacin as an antibacterial model drug. Physicochemical characterizations, cytotoxicity evaluation, haemolysis and antibacterial activity studies of the synthesized probe and its ability to target onto bone are demonstrated. Our results indicate that there is significant scope in developing functionalized CDs as theranostic agents.
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    Generation of pH responsive fluorescent nano capsules through simple steps for the oral delivery of low pH susceptible drugs
    (MATERIALS RESEARCH EXPRESS, 2016) Radhakumary, C; Sreenivasan, K
    pH responsive nano capsules are promising as it can encapsulate low pH susceptible drugs like insulin and guard them from the hostile environments in the intestinal tract. The strong acidity of the gastrointestinal tract and the presence of proteolytic enzymes are the tumbling blocks for the design of drug delivery vehicles through oral route for drugs like insulin. Nano capsules are normally built over templates which are subsequently removed by further steps. Such processes are complex and often lead into deformed and collapsed capsules. In this study, we choose calcium carbonate (CaCO3) nano particles to serve as template. Over CaCO3 nanoparticles, silica layers were built followed by polymethacrylic acid chains to acquire pH responsiveness. During the polymerization process of the methacrylic acid, the calcium carbonate core particles were dissolved leading to the formation of nano hollow capsules having a size that ranges from 225 to 246 nm and thickness from 19 to 58 nm. The methodology is simple and devoid of additional steps. The nano shells exhibited 80% release of the loaded model drug, insulin at pH 7.4 while at pH 2.0 the capsules nearly stopped the release of the drug. Polymethacrylic acid shows pH responsive swelling behavior that it swells at intestinal pH (7.0-7.5) and shrinks at gastric pH (similar to 2.0) thus enabling the safe unloading of the drug from the nano capsules.
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    Gentamicin induced formation of gold nanoparticles as an assay protocol for its detection
    (COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS, 2014) Radhakumary, C; Sreenivasan, K
    A quick method for the visualization and estimation of gentamicin up to a concentration of 10 mg L-1 is formulated. Since gentamicin lacks any chromophore or fluorophore, direct spectro photometric or fluorometric estimation cannot be used for the detection of this widely used antibiotic. Here we explored the ability of gentamicin to reduce gold ions into gold nanoparticles. The formation of the wine red colored gentamicin stabilized gold colloid (Au-genta) from the colorless aqueous gentamicin solution made it possible its detection with both naked eye and spectrophotometrically. This method does not need any tedious chemical derivatization or fluorescent labeling steps or the use of any costly instrumental analysis techniques. It also offers comparatively better sensitivity (2.5 mg L-1) than the other reported methods (390 mg L-1 for gentamicin derivatization with ninhydrin and 1000 mg L-1 with o-phthalaldehyde). (C) 2013 Elsevier B.V. All rights reserved.
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    Gentamicin induced formation of gold nanoparticles as an assay protocol for its detection.
    (Colloids and Surfaces A., 2013-12) Radhakumary, C; Sreenivasan, K
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    Graft copolymerization of 2-hydroxy ethyl methacrylate onto chitosan with cerium (IV) ion. I. Synthesis and characterization
    (JOURNAL OF MACROMOLECULAR SCIENCE-PURE AND APPLIED CHEMISTRY, 2003) Radhakumary, C; Divya, G; Nair, PD; Mathew, S; Nair, CPR
    Graft copolymerization of 2-Hydroxy ethyl methacrylate (HEMA) on to chitosan was studied using cerium (IV) as the initiator. Optimization of the grafting was worked out by varying the reaction time and monomer concentration. Under controlled conditions, up to 685% grafting with a grafting yield of 92.4% was achieved. FTIR, thermal and XRD techniques were used to confirm the formation of the grafted copolymer. Grafting caused a marginal decrease in the mechanical strength in the dry conditions and a significant decrease under wet conditions for the resultant polymer. The products showed significantly improved swelling at pH 7.4 and pH 1.98 compared to the original chitosan. Grafted polymer showed enhanced Tg and decomposition temperature. The grafting also resulted in improved hydrophilicity as is evident from the contact angle studies of the films.
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    HEMA-grafted chitosan for dialysis membrane applications
    (JOURNAL OF APPLIED POLYMER SCIENCE, 2006) Radhakumary, C; Nair, PD; Mathew, S; Nair, CPR
    Chitosan was graft copolymerized with HEMA (2-Hydroxyethylmethacrylate) for the development of blood-compatible dialysis membranes. The permeation characteristics of HEMA-grafted chitosan films for four different solutes creatinine, urea, glucose, and albumin was studied in vitro at 37 C for assessment of the suitability as dialysis membranes. The grafted film CH-12.5 composition (425% grafting) showed very high permeation to creatinine by reaching the equilibrium within 45 min. The compositions CH-7.5 and CH-12.5 showed excellent permeation to glucose when compared to virgin chitosan films. In the case of urea permeation, all the grafted compositions exhibited higher percent permeation than the virgin chitosan films. The copolymer films CH-7.5 and CH-12.5 showed enhanced permeability for the high molecular weight solute, albumin. The other grafted copolymer compositions followed almost the same trend as that of chitosan for the low molecular weight solutes as well as the high molecular weight solute. The copolymer films were also found to be highly blood compatible, noncytotoxic, and biodegradable. Hence, the need for developing blood-compatible chitosan membranes with desirable permeability properties is achieved by the graft copolymerization of HEMA onto chitosan. (c) 2006 Wiley Periodicals, Inc.
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    Hyaluronic acid-g-poly(HEMA) copolymer with potential implications for lung tissue engineering
    (CARBOHYDRATE POLYMERS, 2011) Radhakumary, C; Nandkumar, AM; Nair, PD
    Tissue engineering represents an attractive potential for regeneration of engineered functional pulmonary tissue. Hyaluronic acid, an extracellular matrix component promotes the growth and proliferation of most cells. The high water affinity of hyaluronic acid (HA) adversely affects its application in the field of tissue engineering. A copolymer of hyaluronic acid and poly(2-hydroxyethylmethacrylate). [poly(HEMA)] appeared as a good choice for the synthesis of a natural-synthetic polymer hybrid matrix with the synergistic properties of both the polymers like water stability and biocompatibility. The copolymer films were stable in water at both acidic and neutral pH in contrast to that of virgin HA films. Grafting significantly alters the mechanical properties of hyaluronic acid. The HA-g-poly(HEMA) is found to be non-cytotoxic to mammalian cells. Further, the polymer was analysed for supporting alveolar cell adhesion and growth and were found suitable for supporting multiple cell types with specific culture requirements. Thus, grafting with poly(HEMA) is a suitable method for the fabrication of stable, cytocompatible natural-synthetic polymer hybrid matrices for varied biomedical applications such as tissue engineering, wound dressings, drug delivery and so forth. (C) 2011 Elsevier Ltd. All rights reserved.
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    In vitro detection of calcium in bone by modified carbon dots
    (ANALYST, 2013) Krishna, AS; Radhakumary, C; Sreenivasan, K
    This article depicts a simple and novel approach to locate calcium deposits in bone using modified carbon dots (CDs) through fluorescence imaging. Amino-functionalized CDs along with glutamic acid, a naturally-occurring ligand for calcium ions, were conjugated onto hyaluronic acid using EDC chemistry. The ability of the probe to recognise Ca ions was demonstrated using polymer strips doped with Ca ions and freshly collected bones. The probe was found to bind more at bone cracks, reflecting its potential to locate micro-cracks in bone as well as to map Ca deposits. The bound portions can be visualized through a fluorescence microscope or by illumination by a UV source (365 nm). The components used to generate the probes, namely CD, glutamic acid and hyaluronic acid, are well known for their non-toxicity and biocompatibility. It appears, therefore, that the probe could be used for in vivo applications.
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    In vitro detection of calcium in bone by modified carbon dots.
    (Analyst., 2013-10) Krishna, AS; Radhakumary, C; Sreenivasan, K
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    Methotrexate anchored carbon dots as theranostic probes: digitonin conjugation enhances cellular uptake and cytotoxicity
    (RSC Advances, 2016-06) Krishna, AS; Radhakumary, C; Priya, SS; Ramesan, RM; Sreenivasan, K
    In recent years carbon dots (CDs) have been drawing increasing attention in the area of nano medicine. Their indubitable roles in cellular imaging, drug delivery and diagnosis are widely acknowledged. Digitonin (DG) has traditionally been known as a cell membrane permeabilizing agent. Based on this fact, we modified CDs with DG (CDDG) and further conjugated them with methotrexate (MX). This probe, CDDG conjugated MX (CDMX) was subjected to physico chemical characterization, cytotoxic evaluation via MTT assay and cellular uptake studies using confocal laser microscopy. The drug release study implied that at physiological pH, release is less reflecting maximum drug retention in the probe during circulation. The results which emerged have shown that DG is impacted in enhancing cellular uptake and cytotoxic potential of the drug carriers. The study indicates that theranostic probes with improved features can be generated from CDs by a judicious modification
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    On the observation of the need for an unusually high concentration of Cysteine and Homocysteine to Induce Aggregation of Polymer stabilized Gold Nano Particles
    (J Nanopart Res., 2013-01) Radhakumary, C; Sreenivasan, K
    This study reports the interaction of chitosan-stabilized gold nanoparticles (CH-AuNPs) with cysteine (Cys) and homocysteine (Hcys) in aqueous media at pH 1.4. Since the polymer precipitates at higher pH, and the amino acids Cys and HCys are soluble at acidic pH, we kept the pH around 1.4 for stabilizing the particles. Zeta potential of CH-AuNPs was found to be positive and it is reasonable to assume that +ve Cys or Hcys at pH 1.4 will experience repulsive force. However, TEM images and absorption spectra indicated formation of aggregates including rod-like assembly. An interesting observation was the need for unusually high concentration of analytes (Cys and Hcys) to induce the assembly of CH-AuNPs. We also found time bound variation of the optical properties probably indicating the interaction is kinetically controlled and only a fraction of the analyte molecules having sufficient energy can bind onto the particles. We observed that at elevated temperature, the reaction was faster with a lower concentration of Cys or Hcys. These observations were supported by the classical Derjaguin–Landau–Verwey–Overbeek (DLVO) theory which describes the interparticle interaction and the colloidal stability in solution. Only molecules possessing enough energy to cross this force barrier can cause the aggregation. We also noted a time lag between Cys and Hcys to influence optical properties reflecting the possibility of using this simple approach to discriminate these two clinically relevant molecules. Our observation shows that simple sensing as well as generation of novel nanostructures could be manipulated by a judicious choice of conditions such as stabilizing agents, pH, etc.
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    On the observation of the need for an unusually high concentration of cysteine and homocysteine to induce aggregation of polymer-stabilized gold nano particles
    (JOURNAL OF NANOPARTICLE RESEARCH, 2013) Radhakumary, C; Sreenivasan, K
    This study reports the interaction of chitosan-stabilized gold nanoparticles (CH-AuNPs) with cysteine (Cys) and homocysteine (Hcys) in aqueous media at pH 1.4. Since the polymer precipitates at higher pH, and the amino acids Cys and HCys are soluble at acidic pH, we kept the pH around 1.4 for stabilizing the particles. Zeta potential of CH-AuNPs was found to be positive and it is reasonable to assume that +ve Cys or Hcys at pH 1.4 will experience repulsive force. However, TEM images and absorption spectra indicated formation of aggregates including rod-like assembly. An interesting observation was the need for unusually high concentration of analytes (Cys and Hcys) to induce the assembly of CH-AuNPs. We also found time bound variation of the optical properties probably indicating the interaction is kinetically controlled and only a fraction of the analyte molecules having sufficient energy can bind onto the particles. We observed that at elevated temperature, the reaction was faster with a lower concentration of Cys or Hcys. These observations were supported by the classical Derjaguin-Landau-Verwey-Overbeek (DLVO) theory which describes the interparticle interaction and the colloidal stability in solution. Only molecules possessing enough energy to cross this force barrier can cause the aggregation. We also noted a time lag between Cys and Hcys to influence optical properties reflecting the possibility of using this simple approach to discriminate these two clinically relevant molecules. Our observation shows that simple sensing as well as generation of novel nanostructures could be manipulated by a judicious choice of conditions such as stabilizing agents, pH, etc.
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    Pattern of cardiac fibrosis in rabbits periodically fed a magnesium-restricted diet and administered rare earth chloride through drinking water
    (BIOLOGICAL TRACE ELEMENT RESEARCH, 1998)
    It has been postulated that causation of the tropical cardiomyopathy endomyocardial fibrosis (EMF) is linked to magnesium (Mg) deficiency and cardiac toxicity of the rare earth element cerium (Ce). The aim of the present study was to define the myocardial lesions in rabbits that were fed on Mg-restricted diet (70-80 ppm) periodically and were provided drinking water contaminated with rare earth chloride (1 g/L). Forty New Zealand white rabbits were divided into four groups following a 2 x 2 factorial design. Two groups were periodically fed on Mg-restricted diet with one of them receiving water contaminated with rare earth chloride. The other two groups were continuously fed on Mg-sufficient diet (350-400 ppm) with one of them receiving water contaminated with rare earth chloride. AU animals were sacrificed at the end of 6 mo. Cardiac tissues were subjected to histology, elemental analysis (calcium [Ca], Mg, and Ce) and estimation of collagen content and collagen phenotypes. Histological lesions were compared with those of EMF in humans and those of acute Mg deficiency in animals. The results suggest that in rabbits, recurrent episodes of Mg deficiency lead to myocardial fibrosis similar to the pattern observed in human EMF.