C M Gupta

Aligarh Muslim University, Alīgarh, Uttar Pradesh, India

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Publications (43)150.97 Total impact

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    M Owais, C M Gupta
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    ABSTRACT: Successful homing of drugs to the desired biological compartment of the host usually depends on the intrinsic properties of the drug molecules. However, it can always be manipulated by appropriate designing of the carrier/delivery system, as little can be done to influence the target and its surroundings. Various carrier systems have emerged to deliver drugs to macrophages, albeit the efficacy, reliability and selectivity of these carriers are still in question. To date, the most extensively studied carriers are liposomes and microspheres. In fact, physicochemical properties of these carriers can alter their efficacy and specificity to a great extent. These properties include hydrophilicity, surface charge, composition, concentration, and presence of various target specific ligands on their surface. Incidentally, the particulate nature of these vehicles may facilitate passive homing of the entrapped drug molecules to the macrophages, which may harbour many of the important pathogens in their intracellular compartments, such as Mycobacterium sps, Leishmania and dengue virus etc., belonging to three different major classes of microbes. Moreover, macrophages upon interaction with particulate drug delivery vehicles may act as secondary drug depot, thus helping in localized delivery of the drug at the infected site. In the present article, a comprehensive review of literature is presented on the suitability of some lipid-based and polymeric materials as vehicles in delivery of drugs to macrophages in parasitic infections.
    Current Drug Delivery 11/2005; 2(4):311-8.
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    C M Gupta, W Haq
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    ABSTRACT: Tuftsin is a tetrapeptide (Thr-Lys-Pro-Arg) that specifically binds monocytes, macrophages, and polymorphonuclear leukocytes and potentiates their natural killer activity against tumors and pathogens. The antimicrobial activity of this peptide is significantly increased by attaching at the C-terminus a fatty acyl residue through the ethylenediamine spacer arm. This activity is further augmented by incorporating the modified tuftsin in the liposomes. The tuftsin-bearing liposomes not only enhance the host's resistance against a variety of infections but also serve as useful vehicles for the site-specific delivery of drugs in a variety of macrophage-based infections, such as tuberculosis and leishmaniasis.
    Methods in Enzymology 02/2005; 391:291-304. · 2.00 Impact Factor
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    ABSTRACT: In the present study, we evaluated the potential of an immunomodulator tuftsin in increasing the efficacy of liposomised diethylcarbamazine (DEC) against experimental filarial infection of Brugia malayi. The liposomised form of DEC, when used at sub-optimal dose of 25 mg/kg body weight, successfully eliminated filarial parasite from systemic circulation in animals inflicted with B. malayi infection. However, the formulation was effective upto 60 days post infection only, followed by recurrence of the infection. In contrast, the co-administration of liposomal formulation of DEC along with an immunomodulator tuftsin was found to be competent enough to suppress microfilarial stage of parasite till 90 days post treatment. Interestingly, tuftsin bearing DEC liposomes were found to be effective against adult parasite as well.
    Journal of Drug Targeting 05/2003; 11(4):247-51. · 2.77 Impact Factor
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    ABSTRACT: Chemotherapeutic efficacy of the amphotericin B (Amp B), which is the drug of choice for treatment of the leishmanial infections (kala-azar) that become resistant to the conventional chemotherapy using antimonials, has been examined in the Leishmania donovani infected hamsters after encapsulating the drug in tuftsin-free as well as tuftsin-bearing liposomes. The activity was significantly increased (p < 0.05) by delivering Amp B in tuftsin-free liposomes. This antileishmanial effect of the liposomized Amp B was further increased (p < 0.05) by grafting the natural macrophage-activator tetrapeptide, tuftsin (Thr-Lys-Pro-Arg), on the liposome's surface. This could possibly be attributed to both the enhanced drug tolerance after liposomization as well as to the increased uptake of tuftsin-bearing Amp B-laden liposomes by the macrophages. In addition to the increased efficacy, encapsulation of Amp B in the tuftsin-bearing liposomes also enhanced the drug accessibility to areas (e.g. bone marrow) that are otherwise inaccessible to the free drug. These results further demonstrate the usefulness of tuftsin-bearing liposomes as drug vehicles in treatment of the macrophage-based infections that have been reviewed recently (Agrawal, A.K. and Gupta, C.M. (2000). Tuftsin-bearing liposomes in treatment of macrophage-based infections, Adv. Drug Deliv. Rev., 41, 135-146).
    Journal of Drug Targeting 02/2002; 10(1):41-5. · 2.77 Impact Factor
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    A K Agrawal, A Puri, W Haq, C M Gupta
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    ABSTRACT: The immunostimulant activity of non-pyrogenic, sugar-free immunomodulator lipopeptide, Ala-D-Glu(Gly-Lys-CO.C11H23)-NH2 (comp. no 84/201), and its liposomized formulation has been studied. Liposomization of this lipopeptide significantly enhanced its antigen specific as well as nonspecific immune responses, as compared to the free lipopeptide. The liposomized formulation of lipopeptide significantly stimulated both the antibody and delayed-type hypersensitivity responses in Balb/c mice, and also enhanced nonspecifically the macrophage migration index, phagocytic activity and incorporation of 14C glucosamine in peritoneal macrophages of the mice that received pretreatment with this preparation. Further, the mice that received pretreatment with the liposomized preparation strongly resisted lethal P. berghei infection and consequently survived for longer period of times. These results indicate that liposomization of the compound no 84/201 significantly improves its ability to enhance not only antigen-specific immune response but also the nonspecific host's resistance against infections.
    Journal of Drug Targeting 02/2001; 9(4):231-9. · 2.77 Impact Factor
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    ABSTRACT: Liposomes have been widely used to deliver antigens to the antigen-presenting cells (APCs) and also to modify their immunological behaviour in model animals. We recently demonstrated the potential of yeast lipid liposomes to undergo membrane-membrane fusion with cytoplasmic membrane of the target cells. Interestingly, studies in the present report revealed that antigen encapsulated in yeast lipid liposomes could be successfully delivered simultaneously into the cytosolic as well as endosomal processing pathways of APCs, leading to the generation of both CD4+ T helper and CD8+ cytotoxic T cells. In contrast, encapsulation of same antigen in egg phosphatidyl-choline (PC) liposomes, just like its free form, has inefficient access to the cytosolic pathway of major histocompatibility complex (MHC) I dependent antigen presentation and failed to generate antigen specific CD8+ cytotoxic T-cell response. However, both egg PC as well as yeast lipid liposomes have elicited strong antigen specific antibody responses in immunized animals. These results imply usage of liposome encapsulated antigen as potential candidate vaccine capable of eliciting both cell mediated as well as humoral immune responses.
    Scandinavian Journal of Immunology 01/2001; 54(1-2):125-32. · 2.20 Impact Factor
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    M Owais, C M Gupta
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    ABSTRACT: In the majority of bacterial and viral infections the generation of cytotoxic T cells is of particular interest because such pathogens are able to escape the host defence mechanisms by surviving intracellularly within the phagocytic cells. To generate a CD8+ T lymphocyte response against exogenous antigens, the prerequisite is their delivery into the cytosol followed by processing and presentation along with class I major histocompatibility complex (MHC-I) molecules. In the present study we describe the method of liposome-based delivery of antigens and other macromolecules into the cytosol of target cells. To develop safe and effective methods for generating CD8+ T lymphocytes, we exploited the fusogenic character of lipids derived from lower organisms, that is baker's yeast (Saccharomyces cerevisiae). The degree of fusion with model membrane systems using yeast lipid liposomes varied from 40-70%, as opposed to 1-8% observed with egg PtdCho liposomes, depending on the assay system used. The fusion of yeast lipid liposomes with macrophages resulted in effective delivery of the entrapped solutes into the cytoplasmic compartment. This was further supported by the inhibition of cellular protein synthesis in J774 A1 cells by ricin A, encapsulated in the yeast lipid liposomes. Interestingly, the model antigen ovalbumin, when entrapped in the yeast lipid liposomes, successfully elicited antigen reactive CD8+ T cell responses. It may be concluded that the liposomes made of lipids derived from S. cerevisiae can spontaneously fuse with macrophages, delivering a significant portion of their contents into the cytoplasmic compartment of the cells.
    European Journal of Biochemistry 08/2000; 267(13):3946-56. · 3.58 Impact Factor
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    A K Agrawal, C M Gupta
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    ABSTRACT: The use of liposomes as drug carriers in treatment of various diseases has been explored extensively for more than 20 years. 'Conventional' liposomes, when administered in vivo by a variety of routes, rapidly accumulate in the mononuclear phagocyte system (MPS). The inherent tendency of the liposomes to concentrate in MPS can be exploited in enhancing the non-specific host defence against infections by entrapping in them the macrophage modulators, and as carriers of antibiotics in treatment of intracellular infections that reside in MPS. This must further be enhanced by grafting on the liposome surface the ligands, e.g. tuftsin, that not only binds specifically to the MPS cells but also enhances their natural killer activity. Keeping this in view, we designed and developed tuftsin-bearing liposomes as drug carriers for the treatment of macrophage-based infections and outline these studies in this overview.
    Advanced Drug Delivery Reviews 04/2000; 41(2):135-46. · 12.89 Impact Factor
  • A K Agrawal, C M Gupta
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    ABSTRACT: Malaria is a serious public health problem that affects about 300-500 million people and claims 1.5-2.7 million deaths every year. One-third of all humans live in zones where they risk catching it (1). The situation is aggravated because the malarial parasites are rapidly developing resistance to the existing antimalarial drugs, like chloroquine (2), when given in classical pharmaceutical forms. Studies on the molecular basis of chloroquine resistance suggest that enhanced active efflux of the drug from the cells infected with resistant parasite strain prevents drug accumulation to toxic levels within the cytosol of the infected erythrocytes (3-5). It has been shown that erythrocytes infected with chloroquine-resistant parasite accumulate less chloroquine than those with sensitive parasites (6,7). Furthermore, inhibiting the chloroquine efflux by Ca(2+)-channel blockers render the resistant cells fully sensitive to chloroquine (8), indicating that the antimalarial activity of the chloroquine is directly related to its concentration within the parasite food vacuole (9). The mechanism by which this concentration effect is achieved is unclear, but it is believed to involve binding to a putative chloroquine receptor (10).
    Methods in molecular medicine 01/2000; 25:227-39.
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    ABSTRACT: Liposomes have been used to modify the immunological behaviour of a number of antigens. The present study was designed to evaluate the effect of liposomization of ovalbumin on the induction of Th-1 and Th-2-cell response by monitoring the secretion of lymphokines and IgG Isotypes. Liposomes having varied physicochemical properties (positively and negatively charged, neutral and pH-sensitive) were used for this purpose. Ovalbumin delivered in this way induced preferential secretion of IL-4 and production of antigen-specific IgG1 isotypes. This was observed irrespective of the surface charge properties of the liposomes. Further, the concentration of antigen required for the activation of Th cells was 10(2)- to 10(3)-fold lower after encapsulating it in liposomes. These results suggest that liposomes may prove useful adjuvants to prime Th2-like immune responses.
    Cytokines and molecular therapy 04/1996; 2(1):59-65.
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    ABSTRACT: The suitability of liposomes as drug carriers in the treatment of drug-resistant rodent malaria was examined after covalently attaching F(ab')2 fragments of a mouse monoclonal antibody (MAb), MAb F10, raised against the host cell membranes isolated from the Plasmodium berghei-infected mouse erythrocytes, to the liposome surface. The antibody-bearing liposomes thus formed specifically recognized the P. berghei-infected mouse erythrocytes under both in vitro and in vivo conditions. No such specific binding of the liposomes with the infected cells was observed when MAb F10 was replaced by another mouse monoclonal antibody, MAb D2. Upon loading with the antimalarial drug chloroquine, the MAb F10-bearing liposomes effectively controlled not only the chloroquine-susceptible but also the chloroquine-resistant P. berghei infections in mice. The chloroquine delivered in these liposomes intravenously at a dosage of 5 mg/kg of body weight per day on days 4 and 6 postinfection completely cured the animals (75 to 90%) of chloroquine-resistant P. berghei infections. These results indicate that selective homing of chloroquine to malaria-infected erythrocytes may help to cure the chloroquine-resistant malarial infections with low doses of chloroquine.
    Antimicrobial Agents and Chemotherapy 02/1995; 39(1):180-4. · 4.57 Impact Factor
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    ABSTRACT: Encapsulation of amphotericin B in tuftsin-bearing liposomes greatly increased its efficacy in treatment of human aspergillosis in mice. Also, the drug efficacy was significantly increased by pretreating the animals with drug-free tuftsin-bearing liposomes. These results demonstrate that macrophage activation can considerably enhance the therapeutic efficacy of antifungal drugs, like amphotericin B.
    FEBS Letters 08/1993; 326(1-3):56-8. · 3.58 Impact Factor
  • N Singh, R K Jain, C M Gupta, N Anand
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    ABSTRACT: N-Acetylmuramyl-L-alanyl-D-isoglutamine and some of its derivatives have been examined for anti-stress activity. Amongst these, N-palmitoylmuramyl-L-alanyl-D-isoglutamine is shown to considerably enhance the capacity of animals to endure various types of stress. This indicates that besides acting as immunomodulators and sleep regulators, muramyl dipeptides may also act as anti-stress agents.
    Indian journal of experimental biology 08/1990; 28(7):686-7. · 1.20 Impact Factor
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    ABSTRACT: The efficacy of sodium stibogluconate against Leishmania donovani infections was markedly enhanced by encapsulating this drug in tuftsin-bearing liposomes. Also, pretreatment of the animals with these liposomes (free of drug) rendered them resistant to this infection, possibly by activating the host's macrophages. These results demonstrate that tuftsin-bearing liposomes besides delivering the drug to the target cells could also enhance the nonspecific resistance against infections, thus offering an additional advantage over the use of tuftsin-free liposomes as drug carriers in leishmania therapy.
    FEBS Letters 04/1989; 245(1-2):204-8. · 3.58 Impact Factor
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    ABSTRACT: The antifilarial activity of combination of diethylcarbamazine (DEC) and an immunomodulator, N-Palmitoylmuramyl-L-alanyl-D-isoglutamine (NP-MDP) was evaluated against Litomosoides carinii in cotton rat (Sigmodon hispidus) and Mastomys natalensis. DEC was used at 6 mg/kg in cotton rat whereas it was 75 mg/kg x 5 days in mastomys. The immunomodulator was administered at 62.5 to 500 micrograms/animal x 2 days. Combination therapy with optimum dose of immunomodulator resulted in prolonged and significant suppression of microfilaraemia in comparison to infected animals treated only with DEC. The effective doses of immunomodulator alone or in combination with DEC also caused enhanced antibody titre in treated animals. Though combination therapy resulted in prolonged suppression of microfilaraemia, the effect disappeared slowly and caused no damage to adult worms.
    The Japanese journal of experimental medicine 01/1989; 58(6):243-8.
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    A K Agrawal, A Singhal, C M Gupta
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    ABSTRACT: Covalent attachment of anti-erythrocyte F(ab')2 to the liposome surface has recently been shown to considerably enhance the liposome binding to erythrocytes in vivo. These antibody bearing liposomes have now been found quite effective as vehicles for delivering the antimalarial drug, chloroquine, to erythrocytes in Plasmodium berghei-infected mice. This demonstrates the usefulness of antibody targeted liposomes as carriers for site-specific drug delivery.
    Biochemical and Biophysical Research Communications 11/1987; 148(1):357-61. · 2.28 Impact Factor
  • K Agarwal, A Bali, C M Gupta
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    ABSTRACT: The phosphatidylcholine (PC) component of liposomes was structurally modified by replacing its C-1, or both C-1 and C-2, ester linkage(s) with an ether and/or carbamyl bond(s) or by changing its steric configuration. Small unilamellar liposomes were formed from PC, traces of the corresponding 14C-labeled PC and cholesterol in the presence of 6-carboxyfluorescein (02.M) by sonication, and purified by centrifugation. These liposomes were administered intravenously to rats, and their stability in blood as well as the rate of their clearance from the circulation were determined. Stability and survival times of liposomes were markedly increased by modifying both the C-1 and the C-2 ester linkages in PC. A similar but quantitatively smaller effect was observed when only the C-1 ester linkage was modified. However, the stability remained unaffected by changing the steric configuration of PC, but this modification influenced the clearance rate of liposomes from the circulation. These results demonstrate that both stability in blood and the clearance rate from circulation can be modulated by structurally modifying the ester linkages in the phospholipid component of liposomes.
    Biochimica et Biophysica Acta 11/1986; 883(3):468-75. · 4.66 Impact Factor
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    C M Gupta, A Puri, R K Jain, A Bali, N Anand
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    ABSTRACT: In Plasmodium berghei infections, the mortality rate and parasitaemias were significantly reduced and the mean survival time was considerably enhanced by pretreating the animals with a tuftsin derivative, Thr-Lys-Pro-ARg-NH-(CH2)2-NHCOC15H31. This effect of the modified tuftsin was further increased upon its incorporation in the liposome bilayer. These results indicate that tuftsin and its derivatives may prove useful in enhancing nonspecific host resistance against protozoan infections.
    FEBS Letters 10/1986; 205(2):351-4. · 3.58 Impact Factor
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    A Singhal, C M Gupta
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    ABSTRACT: Covalent attachment of anti-rat erythrocyte F(ab')2 to liposomes specifically enhanced their binding to rat erythrocytes in vivo and reduced their uptake by the liver. Furthermore, at least 20-30% of the cell-bound liposomes delivered their contents to the cells. Besides, the liposome binding did not affect the survival time of the target cells at least up to 3 h in the blood circulation. These results demonstrate for the first time that liposomes can be successfully targeted to cells other than liver cells in vivo.
    FEBS Letters 07/1986; 201(2):321-6. · 3.58 Impact Factor
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    C X George, R K Jain, C M Gupta, N Anand
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    ABSTRACT: Antiviral activity of an interferon-inducing mycoviral ds RNA against Semliki Forest virus infection was considerably enhanced by N-palmitoylmuramyl-L-alanyl-D-isoglutamine (PMDP), a new muramyl dipeptide. This enhancement in activity was not due to increased production of interferon, but resulted probably from a PMDP-induced increase in nonspecific resistance to infection. These results indicate that a combined treatment with an interferon inducer and muramyl dipeptide may prove highly useful to control effectively viral infections.
    FEBS Letters 06/1986; 200(1):37-41. · 3.58 Impact Factor

Publication Stats

619 Citations
150.97 Total Impact Points

Institutions

  • 2000–2005
    • Aligarh Muslim University
      • Interdisciplinary Biotechnology Unit
      Alīgarh, Uttar Pradesh, India
    • GW Pharmaceuticals plc
      New Sarum, England, United Kingdom
  • 1981–2005
    • Central Drug Research Institute
      • • Biochemistry Division (CDRI)
      • • Parasitology Division (CDRI)
      Lakhnau, Uttar Pradesh, India
  • 1993–1995
    • Institute of Microbial Technology
      Chandigarh, Chandīgarh, India
  • 1990
    • King George's Medical University
      Lakhnau, Uttar Pradesh, India
  • 1979–1981
    • Massachusetts Institute of Technology
      • Department of Biology
      Cambridge, Massachusetts, United States