Browsing by Author "Sharma, CP"

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    Acetylsalicylic acid loaded poly(vinyl alcohol) hemodialysis membranes: Effect of drug release on blood compatibility and permeability
    (JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION, 1997)
    Membranes developed from poly(vinyl alcohol) (PVA) have superior permeability because of the highly hydrophilic character of PVA. However, its blood compatibility needs to be further improved. For this we have developed acetylsalicylic acid (ASA, aspirin) loaded PVA membranes. It seems that the slow release of aspirin from the membrane provides a surface concentration of aspirin sufficient for partially inhibiting platelet adhesion. PVA membrane with 531 mu g cm(-2) of ASA loaded, may be selected for hemodialysis applications. This may help to reduce the amount of heparin infused during hemodialysis, thereby reducing the side-effects associated with the systemic administration of heparin.
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    Activated charcoal microcapsules and their applications
    (JOURNAL OF BIOMATERIALS APPLICATIONS, 1998)
    Activated charcoal, long known to the ancients as a substance of therapeutic value in a variety of maladies, has recently been "rediscovered" to be of great value in medical applications. Activated charcoal hemoperfusion is effective in blood purification for removal of various circulating toxic materials and waste metabolites, directly. However, particulate release and platelet adhesion prevent its continued clinical use. Polymeric coatings or microencapsulation of charcoal within polymers have improved their blood compatibility. Chitosan encapsulated activated charcoal (ACCB) beads have been extensively investigated in our group for the removal of various toxins such as urea, creatinine, uric acid, bilirubin, etc. This article highlights various methods of microencapsulation procedures of activated charcoal and the importance of this novel material for a variety of biomedical applications. Further, this review provides an insight to the future perspectives for using them in clinical practice.
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    Adsorption of human IgG on Cu2+-immobilized cellulose affinity membrane: Preliminary study
    (JOURNAL OF BIOMEDICAL MATERIALS RESEARCH, 2000)
    Immobilized metal ion affinity chromatography (IMAC) is widely used. Transition metal ions have a high affinity to some peptide sequences. We have studied the selective adsorption of human IgG from a mixture of albumin, gamma-globulin, fibrinogen, and IgG onto Cu2+ ion-immobilized cellulose membrane. Although Cu2+ ligand is selective to IgG, in general gamma-globulins also are adsorbed. The simplicity and lower cost of Cu2+ ion-immobilized cellulose membranes may be useful for removing IgG from blood. (C) 2000 John Wiley & Sons, Inc.
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    Aggregation of gold nanoparticles followed by methotrexate release enables Raman imaging of drug delivery
    (J Nanoparticle Res., 2012-10) Durgadas, CV; Sharma, CP; Paul, W; Rekha, MR; Sreenivasan, K
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    Aggregation of gold nanoparticles followed by methotrexate release enables Raman imaging of drug delivery into cancer cells
    (JOURNAL OF NANOPARTICLE RESEARCH, 2012) Durgadas, CV; Sharma, CP; Paul, W; Rekha, MR; Sreenivasan, K
    This study refers an aqueous synthesis of methotrexate (MTX)-conjugated gold nanoparticles (GNPs), their interaction with HepG2 cells, and the use of Raman imaging to observe cellular internalization and drug delivery. GNPs of average size 3.5-5 nm were stabilized using the amine terminated bifunctional biocompatible copolymer and amended by conjugating MTX, an anticancer drug. The nanoparticles were released MTX at a faster rate in acidic pH and subsequently found to form aggregates. The Raman signals of cellular components were found to be enhanced by the aggregated particles enabling the mapping to visualize site-specific drug delivery. The methodology seems to have potential in optimizing the characteristics of nanodrug carriers for emptying the cargo precisely at specified sites.
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    Alginate encapsulated bioadhesive chitosan microspheres for intestinal drug delivery
    (JOURNAL OF BIOMATERIALS APPLICATIONS, 1999) Ramdas, M; Dileep, KJ; Anitha, Y; Paul, W; Sharma, CP
    Sustained intestinal delivery of drugs such as Ei-fluorouracil (choice for colon carcinomas) and insulin (for diabetes mellitus) seems to be a feasible alternative to injection therapy. For successful therapy, the drug should be delivered at proper sites (here, the intestine) for long duration, for producing maximum pharmacological activity. We have attempted to develop a formulation that can bypass the acidity of the stomach and release the loaded drug for long periods into the intestine by using the bioadhesiveness of polyacrylic acid, alginate, and chitosan. Bromothymol blue was taken as a model drug. The formulation exhibited bioadhesive property and released the drug for an eight-day period in vitro.
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    Antibiotic loaded hydroxyapatite osteoconductive implant material - In vitro release studies
    (JOURNAL OF MATERIALS SCIENCE LETTERS, 1995) Paul, W; Sharma, CP
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    Beta cyclodextrin-insulin-encapsulated chitosan/alginate matrix: Oral delivery system
    (JOURNAL OF APPLIED POLYMER SCIENCE, 2000) Moses, LR; Dileep, KJ; Sharma, CP
    Cyclodextrins (CD) form inclusion complexes with many drug molecules. The complexed drugs have increased bioabsorption in in vivo system. We have attempted to complex insulin with P-Cyclodextrin (BCD) and encapsulate in the chitosan/ calcium alginate matrix. For drug release studies insulin complexed with BCD for 20 min and that complexed with BCD for 150 min have been used for encapsulation in the chitosan/calcium alginate matrix. The two matrices seem to have different drug release profiles in simulated intestinal medium (pH 7.4) It appears that drug release from the 20-min BCD complexed system encapsulated in the chitosan/calcium alginate matrix begins only after an hour, where, being released from the 150-min BCD complexed system it begins in the first hour itself. Also, aggregation of the insulin molecules seems to be reduced by the complexation of the drug with BCD. Another noticeable fact is the change in the loading character, which is found to be inversely related to the concentration of BCD when it is above the stoichiometric equivalent of the drug. In an attempt to increase the payload of the drug in the matrix, the pH of the processing medium consisting of calcium chloride and chitosan is varied. It is found that the encapsulation efficiency increases as the pH is decreased from 6.0 to 4.0. Another way of increasing the loading is studied by decreasing the concentration gradient of insulin in the processing alginate solution and the crosslinking medium consisting of chitosan/calcium chloride. Preliminary animal studies on rabbits seem to be promising. (C) 2000 John Wiley & Sons, Inc.
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    Bioadhesive Hydrophobic Chitosan Microparticles for Oral Delivery of Insulin: In Vitro Characterization and In Vivo Uptake Studies
    (JOURNAL OF APPLIED POLYMER SCIENCE, 2011) Sonia, TA; Rekha, MR; Sharma, CP
    Hydrophobically modified polymeric matrices for drug delivery were developed by N-acylation of chitosan with long(C-18) and medium chain(C-8) fatty acid chlorides like octanoyl and oleoyl chloride. Chemical modifications of chitosan were confirmed by IR spectra and trinitrobenzenesulphonic acid assay. Modified chitosan particles were prepared by ionotropic gelation with sodium tripolyphosphate. Hydrophobic modification was confirmed by contact angle measurements. Scanning electron micrographs showed the presence of compact microparticles. Swelling studies showed that oleoyl chitosan exhibited low swelling profile than octanoyl chitosan at acidic pH. In vitro release profile at pH 7.4 showed that about 90% of insulin was released by 5th hour. ELISA studies proved that the microparticles were capable of maintaining biological activity of insulin. Mucoadhesion studies proved that oleoyl derivative was more mucoadhesive than octanoyl derivative. In vivo uptake studies of fluorescent-labeled microparticles on rat intestinal sections showed that oleoyl chitosan microparticles exhibited significant uptake than octanoyl chitosan. These results suggests that oleoyl moiety would resist degradation by the gastric enzymes and will enhance mucoadhesivity through hydrophobic interactions and also the permeability by loosening the tight junctions, thus making it a useful carrier for oral peptide delivery applications. (C) 2010 Wiley Periodicals, Inc. J Appl Polym Sci 119: 2902-2910, 2011
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    Biomimetic mucin modified PLGA nanoparticles for enhanced blood compatibility
    (JOURNAL OF COLLOID AND INTERFACE SCIENCE, 2013) Thasneem, YM; Rekha, MR; Sajeesh, S; Sharma, CP
    Efforts to develop long circulating polymeric nanoparticles have propelled many strategies in nanoparticle surface modification to bypass immune surveillance and systemic clearance. In this context, our present study reports on the preparation and evaluation of mucin functionalized poly lactic-co-glycolic acid (PLGA) nanoparticles as hemocompatible, cell penetrating nanoparticulate drug delivery system. Amino groups of mucin were conjugated to the terminal carboxylic acid groups on PLGA to be followed by nanoparticle synthesis via standard solvent evaporation technique. Detailed in vitro experiments were performed to illustrate the significance of alternating copolymer structured mucin modified PLGA nanoparticles in terms of enhanced hemocompatibility and cellular uptake. Mucylation proved promising in controlling PLGA nanoparticle- interaction with plasma proteins (opsonins) and blood components via hemolysis, thrombogenecity and complement activation. Besides hemocompatibility, the modified and unmodified nanoparticles were also found to be cytocompatible with L929 and C6 cell lines. The fluorescent and confocal image analysis evaluated the extent of cellular uptake of nanoparticles into C6 cells. Specifically the combination of stealth properties and cellular internalization capacity of mucin modified PLGA nanoparticle (PLGA Mucin) lead us to propose it as a safe, efficient and multifunctional nanoplatform for disease specific intravenous drug delivery applications as far as in vitro experiments are concerned. (C) 2013 Elsevier Inc. All rights reserved.
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    Blood protein adsorption and compatibility studies of gold nanoparticles
    (GOLD BULLETIN, 2011) Nimi, N; Paul, W; Sharma, CP
    Gold nanoparticles are considered to be real jewels. The significant growth of their application for labeling, delivery, heating, and sensing shows their significance in biology and/or life sciences. PEGylated gold nanoparticles also have significant application in drug and gene delivery. However, comprehensive information on the compatibility of these nanoparticles to blood is limited in literature. An attempt has been made to study the protein adsorption, blood cell aggregation, and C3 adsorption onto these particles to evaluate its complement activation potential and blood compatibility. It has been observed that these nanoparticles do not induce any complement activation or blood cell aggregation. Particles were non-hemolytic and the adsorptions of proteins were negligible which further validates its significance in drug delivery and gene delivery applications.
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    Blood-compatible materials: A perspective
    (JOURNAL OF BIOMATERIALS APPLICATIONS, 2001)
    The interrelation of physicochemical properties with biological interactions at the interface to understand blood compatibility of materials in contact with blood has been discussed. The bioethics for human experimentation and future research outlook has been projected.
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    Calcium Phosphates as Drug Delivery Systems
    (JOURNAL OF BIOMATERIALS AND TISSUE ENGINEERING, 2012) Victor, SP; Sharma, CP
    Calcium phosphate based ceramics present a unique class of materials for orthopaedic and dental applications owing to their wide range of properties that they posses. The strategy of delivering drugs, proteins and growth factors using calcium phosphate carriers represents the most promising approach to improve their bioavailability, reduce the frequency of administration, and to expand the effective routes of administration for effective treatment of bone diseases. The different phases of calcium phosphates exhibit variable solubility, permeability, roughness and porosity, and are decisive factors of drug loading and adsorption. Further the amazing characteristics of nanophase ceramics suggest that they can be excellent for drug transportation and controlled prolonged release. This chapter focuses on the various types of calcium phosphates, their properties and the different systems that have been used for drug and antibiotic delivery. These different forms of micro and nano calcium orthophosphates have great potential as effective carriers of antibiotics, drugs and growth factors to revolutionize the field of hard tissue engineering.
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    Cell mimetic lateral stabilization of outer cell mimetic bilayer on polymer surfaces by peptide bonding and their blood compatibility
    (JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A, 2006) Kaladhar, K; Sharma, CP
    The biological lipid bilayer membranes are stabilized laterally with the help of integral proteins. We have simulated this with an optimized ternary phospholipid/glycolipid/cholesterol system, and stabilized laterally on functionalized poly methyl methacrylate (PMMA) surfaces, using albumin, heparin, and polyethylene glycol as anchors. We have earlier demonstrated the differences due to orientation and packing of the ternary phospholipid monolayers in relation to blood compatibility (Kaladhar and Sharma, Langmuir 2004;20:11115-11122). The structure of albumin is changed here to expose its interior hydrophobic core by treating with organic solvent. The interaction between the hydrophobic core of the albumin molecule and the hydrophobic core of the lipid molecules is confirmed by incorporating the molecule into bilayer membranes. The secondary structure of the membrane incorporated albumin is studied by CD spectral analysis. The structure of the altered albumin molecule contains more beta-sheet as compared to the native albumin. This conformation is also retained in membranes. The partitioning of the different anchors based on its polarity and ionic interactions in the monolayer is studied from the pressure-area (pi-A) isotherm of the lipid monolayers at the air/water interface using Langmuir-Blodgett (LB) trough facility. Such two monolayers are deposited onto the functionalized PMMA surface using LB trough and crosslinked by carbodiimide chemistry. The structure of the deposited bilayer is studied by depth analysis using contact mode AFM in dry conditions. The stabilized bilayer shows stability up to 1 month by contact angle studies. Preliminary blood compatibility studies reveal that the calcification, protein adsorption, as well as blood-cell adhesion is significantly reduced after the surface modification. The reduced adsorption of ions, proteins, and cells to the modified surfaces may be due to the fluidity of the microenvironment along with the contribution of the mobile PEG groups at the surface and the phosphorylcholine groups of the phospholipids. The stability of the anchored bilayer under low shear stress conditions promises that the laterally stabilized supported bilayer system can be used for low shear applications like small diameter vascular graft and modification of biosensors, and so forth. (c) 2006 Wiley Periodicals, Inc.
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    Cell-mimetic coatings for immune spheres
    (COLLOIDS AND SURFACES B-BIOINTERFACES, 2014) Kaladhar, K; Renz, H; Sharma, CP
    Extrinsically induced or engineered cells are providing new therapeutic means in emerging fields such as cell therapeutics, immunomodulation and regenerative medicine. We are demonstrating a spatial induction method using lipid coatings, which can change signal presentation strength from material surface to adherent macrophage cells, that induce early cell-cell interaction leading to organotypic morphology. For that, we have developed a cell mimetic lipid coating with a rafts size to the order of transmembrane proteins (<10 nm) with enhanced lateral elastic properties. Such surface coatings are capable of reducing adherent macrophage spreading, while enabling early induction of cell-cell interaction to form organotypic macrophage colonies or "spheres" (M-spheres). (C) 2014 Elsevier B.V. All rights reserved.
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    Ceramic drug delivery: A perspective
    (JOURNAL OF BIOMATERIALS APPLICATIONS, 2003)
    Different ceramic substances are offered in the market as bone substitute materials. These include monophasic calcium phosphate ceramics of tricalciumphosphate (TCP) or hydroxyapatite (HA), biphasic calcium phosphate ceramics and multiphasic bio-glasses synthetic calcium phosphate cements. Ceramics with appropriate three-dimensional geometry are able to bind and concentrate bone morphogenetic proteins in circulation and may become osteoinductive (capable of osteogenesis) and can be effective carriers of bioactive peptide or bone cell seeds and are therefore potentially useful in tissue engineering and drug delivery. An attempt has been made to review various drug delivery applications of ceramics.
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    Changes in polyurethane calcification due to antibiotics
    (ARTIFICIAL ORGANS, 1996)
    To develop artificial materials for prolonged use in the vascular system, the complicated process of surface-induced calcification must be better understood. Calcification was examined on porous polyurethane incubated in metastable solutions of calcium phosphate, and the role of certain antibiotics in the medium was evaluated. It seems that certain aminoglycoside antibiotics can modify polyurethane surfaces and, subsequently, their mineralization process. In addition, these antibiotics may alter the calcium transport through polyurethanes. Therefore, it is conceivable that certain antibiotics can, in addition to producing their antibacterial effect, modulate surface calcium binding by changing the calcium mobilization and crystallization. Additional studies are needed to develop applications.
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    Chitin and chitosan polymers: Chemistry, solubility and fiber formation
    (PROGRESS IN POLYMER SCIENCE, 2009) Pillai, CKS; Paul, W; Sharma, CP
    Chitin and chitosan (CS) are biopolymers having immense structural possibilities for chemical and mechanical modifications to generate novel properties, functions and applications especially in biomedical area. Despite its huge availability, the utilization of chitin has been restricted by its intractability and insolubility. The fact that chitin is as an effective material for sutures essentially because of its biocompatibility, biodegradability and non-toxicity together with its antimicrobial activity and low immunogenicity, points to immense potential for future development. This review discusses the various attempts reported on solving this problem from the point of view of the chemistry and the structure of these polymers highlighting the drawbacks and advantages of each method and proposes that based on considerations of structure-property relations, it is possible to obtain chitin fibers with improved strength by making use of their nanostructures and/or mesophase properties of chitin. (C) 2009 Elsevier Ltd. All rights reserved.
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    Chitosan and Its Derivatives for Drug Delivery Perspective
    (CHITOSAN FOR BIOMATERIALS I, 2011) Sonia, TA; Sharma, CP
    Biopolymers are promising materials in the delivery of protein drugs due to their compatibility, degradation behavior, and nontoxic nature on administration. On suitable chemical modification, these polymers can provide better materials for drug delivery systems. Nanostructured drug carriers allow the delivery of not only small-molecule drugs but also of nucleic acids and proteins. The use of biopolymers like dextran, starch, alginate, and pullulan nanoparticles in drug delivery are briefly discussed. Being the only cationic polysaccharide of natural origin, chitosan, a versatile biopolymer of the aminoglucopyran family is being extensively explored for various biomedical and pharmaceutical applications such as drug delivery. In this review, we aim to comprehensively integrate the recent applications of chitosan nano/microparticles in oral and/or buccal delivery, stomach-specific drug delivery, intestinal delivery, colon-specific drug delivery, and gene delivery, giving special emphasis to oral drug delivery.
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    Chitosan scaffold co-cultured with keratinocyte and fibroblast heals full thickness skin wounds in rabbit
    (JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A, 2014) Revi, D; Paul, W; Anilkumar, TV; Sharma, CP
    This study evaluated the modulatory effect of chitosan sponge co-cultured with keratinocyte and fibroblast on wound healing. Dermal fibroblasts and keratinocyte isolated from rabbit skin were co-cultured on chitosan sponge, to fabricate cell-loaded chitosan tissue engineered construct. Full thickness excision wounds created on the rabbit dorsum were treated with three types of graft materials - a noncellular chitosan graft, homologous keratinocyte fibroblast loaded chitosan, and a commercial product. Postgraft skin-wound samples were examined histomorphologically at 7th, 14th, and 28th day after staining with hematoxylin and eosin, picrosirius red and/or immunohistochemistry. Wound healing parameters considered were the extent of re-epithelialization, collagen deposition, and neoangiogenesis. The number of proliferating cells, vimentin positive cells, and alpha smooth muscle actin cells were also quantified. The histology results suggested that the grafts aided wound healing but, the cell-loaded graft induced a differential pattern of healing and had lower scarring tendency. The cell-loaded tissue construct may be useful as a therapeutic graft for treating wounds where there is a total loss of tissue and cells as in burn injury. (C) 2013 Wiley Periodicals, Inc.