Manu Jaggi

Dabur Research Foundation, Ghazibad, Uttar Pradesh, India

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Publications (56)148.75 Total impact

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    Indian journal of experimental biology 03/2015; 53(03):158-163. · 0.75 Impact Factor
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    ABSTRACT: Chyawanprash is an ayurvedic formulation used in Indian traditional medicinal system for its beneficial effect on human health. We investigated the immunostimulatory effects of Chyawanprash (CHY) using in vitro assays evaluating the secretion of cytokines such as Tumor Necrosis Factor-alpha (TNF-α), Interleukin-1beta (IL-1β) and Macrophage Inflammatory Protein-1-alpha (MIP-1-α) from murine bone marrow derived Dendritic Cells (DC) which play pivotal role in immunostimulation. The effects of CHY on phagocytosis in murine macrophages (RAW264.7) and Natural Killer (NK) cell activity were also investigated. At non-cytotoxic concentrations (20-500 μg/ml), CHY enhanced the secretion of all the three cytokines from DC. CHY also stimulated both, macrophage (RAW264.7) as well as NK cell activity, in vitro. In conclusion, the data substantiates the immunoprotective role of CHY at cellular level mediated by immunostimulation in key immune cells viz. dendritic Cells, macrophages and NK cells.
    Indian journal of experimental biology 03/2015; 53(03):158-163. · 0.75 Impact Factor
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    ABSTRACT: Imatinib mesylate has been evaluated for possible potential in treatment of colon cancer in recent times. However, due to significant reporting of P-gp expression in colon cancer, it can come across set back due to MDR. Therefore, in present work the liposomal formulation containing imatinib-bile salt conjugate was developed and investigated for its comparative performance in MDR colon cancer cellsand surface modified with hyaluronic acid for achieving low hemotoxicity with stealth characteristics. Imatinib was successfully conjugated with sodium-deoxycholate by charged conjugation and evaluated through FTIR, DSC and PXRD. The developed conjugate (IM-SD) was encapsulated in liposomes and the conditions were optimized by Box-Behnken statistical design to achieve a size of 56.56±1.23nm along with 99.11±0.89% entrapment efficiency (LIPO). The liposomes were surface modified with hyaluronic acid and the size was enhanced to 159.14±3.2nm (HA-LIPO). Flow cytometric studies demonstrated the enhanced uptake of P-gp substrate rhodamine dye in P-gp positive colo 320 colon cancer cells. In addition, an enhanced cellular internalization of HA-LIPO in CD-44 positive HT-29 and colo 320 cells indicates the targeting attributes of the hyaluronan coated liposomes. Finally, the hyaluronan coated liposomes were also found to have low opsonization activity. Copyright © 2014. Published by Elsevier B.V.
    International Journal of Biological Macromolecules 12/2014; 73. DOI:10.1016/j.ijbiomac.2014.11.026 · 3.10 Impact Factor
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    ABSTRACT: A novel alendronate-hyaluronic acid (AL-HA) graft polymer was synthesized by amide coupling.•AL-HA graft polymer was assembled over irinotecan containing NLC by calcium assisted mineralization.•Low IC50 values in MDR Colo-320 colon cancer cells.•Enhanced uptake was found in P-gp overexpressing Colo-320 cell lines.•In-vitro targeting CD-44 bio-receptor in HT-29 and Colo-320 cells.•Modulation of ATPase pump and MDR1 gene expression in cancer cell lines.
    Colloids and surfaces B: Biointerfaces 10/2014; DOI:10.1016/j.colsurfb.2014.09.062 · 4.29 Impact Factor
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    ABSTRACT: Irinotecan loaded nanostructured lipid carrier (NLC-Ir) was surface decorated with hyaluronic acid graft polymer. Hyaluronic acid is a biocompatible, non-antigenic and hydrophilic, CD-44 ligand that can impart many useful features to the nanocarrier for anticancer drug delivery. The present investigation demonstrated that hyaluronic acid coated HA-NLC had significantly lower haemolytic potential as compared to uncoated NLC. Further, HA-NLC had a reduced plasma protein interaction and low macrophage uptake. The in vivo tumor targeting and pharmacodynamics efficacy of HA-NLC was studied in Ehrlich's Ascites Tumor (EAT) allograft model. Radio scintigraphic biodistribution studies revealed that HA-NLC carrier got accumulated in the tumor tissues in good proportion. Additionally, the content of radioactivity associated with tumor tissues remained constant at 2, 4 and 24h (2.41, 2.48 and 2.47%, respectively), while it got reduced in other organs. Furthermore, tumor to muscle ratio of radioactivity suggested a better accumulation of HA-NLC in tumor tissues that was significantly enhanced (P<0.05) with time. In vivo antitumor activity of hyaluronan coated HA-NLC-Ir was 5.8 and 2.6 times higher as compared to control and free drug solution respectively. Furthermore, encapsulation of irinotecan in HA-NLC-Ir nanocarrier was found to have reduced the thrombocytopenia and neutropenia associated with free irinotecan. Thus, it can be inferred that the hyaluronic acid decorated nanocarrier can provide a haemo-compatible, non-toxic and target based delivery system for the effective management of cancer. Copyright © 2014 Elsevier B.V. All rights reserved.
    Colloids and surfaces B: Biointerfaces 10/2014; DOI:10.1016/j.colsurfb.2014.09.061 · 4.29 Impact Factor
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    ABSTRACT: In present investigation, we developed a novel hyaluronated cationic nanostructured lipid carrier (CNLCs) which contains CPT-11/irinotecan to target CD44 biomarker which commonly overexpresses on colon cancer. The cationic core NLCs was developed by using Capmule MCM and Compritol as mix lipid phase with 150± 2.5nm particles size and 93.98±2.5% entrapment efficiency. The cationic core NLCs were coated with hyaluronic acid by ionic conjugation. The particle size of hyaluronated CNLCs was enhanced to255±4.2nm. In-vitro drug release studies revealed a slow and sustain release of the drug and a practically no leaching of coumarin-6. The confocal laser microscopy studies were performed with developed CNLCs in two CD44 overexpressing cell lines (HT-29 and Colo-320). The studies revealed marked uptake of the CNLCs by both the cell lines in just two hours. The results were comparable to the FITC conjugated CD44 antibodies. Therefore, the developed dual purpose CNLCs were found to be highly specific for CD44 biomarker. The developed formulations were found to be compatible with blood components. The MTT assay revealed that the developed particles had enhanced cytotoxicity against non-MDR as well MDR cancer cells.
    International Journal of Biological Macromolecules 09/2014; 72. DOI:10.1016/j.ijbiomac.2014.09.005 · 3.10 Impact Factor
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    02/2014; 1(1). DOI:10.14440/jbm.2014.12
  • Colloids and surfaces B: Biointerfaces 01/2014; · 4.29 Impact Factor
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    ABSTRACT: Multidrug resistance (MDR) is an area of concern for the drug developers as well as clinical practitioners. This phenomenon is putting an emance pressure on treatment modalities of many diseases as well as posing a grave danger over clinically accepted drugs as well as molecules under clinical development. P-glycoprotein (P-gp) mediated efflux of xenobiotics is one of the major mechanisms involved in MDR. Hence, an effective modulation of P-gp may restore the potential of many substrate drugs. However, the non-specific P-gp modulation may be associated with many unwanted toxic effects. Therefore, an approach involving simultaneous exploitation of P-gp modulation as well as targeted delivery in a particulate carrier system may result in a more effective MDR reversal, accompanying a safer drug profile.
    Medical Hypotheses 12/2013; DOI:10.1016/j.mehy.2013.12.006 · 1.15 Impact Factor
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    ABSTRACT: The present study investigates the screening of the formulation components as well as evaluates the quality issues of the nanostructured lipid carriers (NLCs) for the anticancer agent, CPT-11. The Stepwise screening of the components for the preparation of NLCs requires the selection of liquid lipid or oil, based on the relative solubility of CPT-11 in different oils. Maximum solubility of the CPT-11 was found in capmul MCM-C8 (81± 0.5mg/ml). Hence, it was selected as the liquid lipid for the development of NLCs. Solid lipids gelucire 39/1, glyceryl mono stearate (GSM) and compritol ATO 888 were observed to have good affinity for the drug on systematic screening of different solid lipids. However, gelucire 39/1 and GSM were found to have lower physical compatibility (miscibility) with capmul MCM C-8. Hence, compritol ATO 888 was selected as the solid lipid phase for the preparation of NLCs. Ratio of liquid lipid (oil) to solid lipid was optimized with the intention of maximizing the oil concentration (as oil was found to have higher solubility of drug) as well as producing a lipid mix with sufficient melting point to maintain solid state. The liquid-solid lipid mixture in the ratio up to 30:70 was observed to have sufficient melting point (52.48±1.2°C). Pluronic F-68 was selected as the main surfactant for the preparation of NLCs because of its good emulsification efficacy for the solid lipid liquid mix. The optimized formulation was also evaluated for the different quality issues. PXRD data revealed that the characteristic peaks of the compritol were present in the NLC samples and there was no appreciable polymorphic change when the formulation was stored for 6 months. Electron microscopic and DLS studies proved the absence of different colloidal species. Thermal analysis by DSC revealed that the lipid particles maintained sufficiently good melting point even after nanosizing. Absence of gelation on multiple syringing and resilience for the stress provided by autoclaving further established the quality of the developed NLCs.
    International Journal of Pharmaceutics 12/2013; DOI:10.1016/j.ijpharm.2013.12.006 · 3.79 Impact Factor
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    ABSTRACT: Abstract To develop naphthyridine derivatives as anticancer candidates, pharmacokinetic (PK) evaluations of 10 novel derivatives of 1,4-dihydro-4-oxo-1-proparagyl-1,8-naphthyridine-3-carboxamide, with potent anticancer activity were done using in vitro ADME (absorption, distribution, metabolism, excretion) and pharmacokinetic--pharmcodynamic (PK/PD) assays. Only derivatives 5, 6, 9 and 10 showed better metabolic stability, solubility, permeability, partition coefficient and cytochrome P450 (CYP) inhibition values. PK of derivatives 5, 6, 9 and 10 in rat showed comparable PK profile for derivative 5 (C0 = 6.98 µg/mL) and 6 (C0 = 6.61 µg/mL) with no detectable plasma levels for derivatives 9 and 10 at 5.0 mg/kg i.v. dose. PK/PD assay of derivatives 5 and 6 in tumor-bearing mice (TBM) showed comparable PK but tumor plasma index (TPI) of derivative 6 (4.02) was better than derivative 5 (2.50), suggesting better tumor uptake of derivative 6. Derivative 6, as lead compound, showed highest tumor growth inhibition (TGI) value of 33.6% in human ovary cancer xenograft model.
    Journal of Enzyme Inhibition and Medicinal Chemistry 10/2013; DOI:10.3109/14756366.2013.845817 · 2.38 Impact Factor
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    ABSTRACT: The purpose of this work is intended to investigate the potential of self-nanoemulsifying (SNE) drug delivery system for enhanced oral bioavailability of etoposide by P-glycoprotein (P-gp) modulation. The components of SNE formulation were optimized by their solubilization and emulsification efficiency. The ternary phase diagrams provided nanoemulsion existence ranges and the corresponding formulations were developed and evaluated via thermodynamic and dispersibility tests. The successful formulations were characterized for various parameters including time required for self-emulsification, percentage transmittance, droplet size, surface morphology, zeta potential and in vitro release. The etoposide loaded SNE9 formulation showed 2.6- and 11-fold higher permeability coefficient in apical to basolateral direction across Caco-2 monolayers as compared to the Etosid and plain drug solution, respectively. The etoposide loaded SNE9 formulation showed a higher cytotoxicity at the highest tested concentration compared to the blank SNE9 formulation and the free etoposide. Furthermore, an in vivo pharmacokinetic study of etoposide in SNE9 formulation showed 3.2- and 7.9-fold increase in relative oral bioavailability compared with that of etoposide in Etosid and drug suspension, respectively. Thus, the developed SNE drug delivery system could be a valuable tool for the effective oral delivery of etoposide.
    Journal of Biomedical Nanotechnology 07/2013; 9(7):1216-29. DOI:10.1166/jbn.2013.1613 · 7.58 Impact Factor
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    ABSTRACT: We have previously synthesized a series of 1,8-naphthyridine-3-carboxamide derivatives to identify potential anti-cancer/anti-inflammatory compounds. Three derivatives, 7-chloro-N-(3-(cyclopentylamino)-3-oxo-1-phenylpropyl)-6-fluoro-4-oxo-1-(prop-2-yn-1-yl)-1,4-dihydro-1,8-naphthyridine-3-carboxamide (C-22), 7-chloro-N-(2-hydroxy-3-oxo-1-phenyl-3-(phenylamino)propyl)-4-oxo-1-(prop-2-yn-1-yl)-1,4-dihydro-1,8-naphthyridine-3-carboxamide (C-31) and 7-chloro-6-fluoro-N-(2-hydroxy-3-oxo-1-phenyl-3-(phenylamino)propyl)-4-oxo-1-(prop-2-yn-1-yl)-1,4-dihydro-1,8-naphthyridine-3-carboxamide (C-34) demonstrated high cytotoxicity against a number of cancer cell lines and inhibited secretion of IL-1-β and IL-6. In the present study, C-22, C-31 and C-34 were assessed for modulation of pro-inflammatory cytokines, TNF-α and IL-8, chemokine RANTES and NO produced by lipopolysaccharide (LPS)-treated mouse Dendritic cells (DCs). Among the 3 compounds, C-34 showed the most potent inhibition of inflammatory markers in DC model at 0.2 and 2μM. C-34 also significantly downregulated the secretion of TNF-α, IL-1-β and IL-6 by murine splenocytes and THP-1 cells against LPS induced levels. In vitro effects of C-34 on bone marrow toxicity were assessed in CFU-GM assay. Human CFU-GM population was comparatively more sensitive to C-34 (0.1-10μM) than murine CFU-GM. IC(50) values for murine and human CFU-GM were not attained. C-34 was further examined for in vivo suppression of LPS induced cytokines in a mice model. At doses ranging from 1.25 to 5mg/kg, C-34 led to significant inhibition of TNF-α, IL-1-β, IL-6 and MIP-1-α. At the highest dose of 5mg/kg, C-34 also protected LPS-treated mice against endotoxin-induced lethality. In conclusion, C-34 demonstrates anti-inflammatory activity in vitro and in vivo in addition to cytotoxic properties. This finding suggests its potential for further development as a synthetic naphthyridine derivative with dual anti-cancer and anti-inflammatory (cytokine inhibition) properties.
    International immunopharmacology 01/2013; DOI:10.1016/j.intimp.2013.01.011 · 2.71 Impact Factor
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    ABSTRACT: The present investigation was aimed to establish a validated stability-indicating liquid chromatographic method for the estimation of etoposide (ETP) in bulk drug and self-nano emulsifying formulation. ETP was successfully separated from the degradation products formed under stress conditions on LiChrospher 100 C18 reverse-phase column (a 250 mm × 4.6 mm i.d., 5-μm particle size) using 55:45 (v/v) acetonitrile-phosphate buffer saline (pH 4.5) as the mobile phase, at a flow rate of 1.0 mL min(-1) and detection at 283 nm. The response was a linear function of analyte concentration (R(2) > 0.9997) over the concentration range of 0.05-50 μg mL(-1). The method was validated for precision, accuracy, robustness, sensitivity and specificity. The % recovery of ETP at three different levels (50%, 100% and 150%) ranged between 93.84% and 100.06% in optimized self-nano emulsifying formulation, Etosid® soft-gelatin capsule and Fytosid® injection. First-order degradation kinetics of ETP were observed under acidic and alkaline conditions. The method was also applied for the stability assessment of self-nano emulsifying formulation under accelerated conditions, the formulation was found to be stable at all storage conditions with the shelf-life of 2.37 years at 25 °C. The method holds promise for routine quality control of ETP in bulk, pharmaceutical formulations as well as in stability-indicating studies.
    Saudi Pharmaceutical Journal 01/2013; 21(1):103-11. DOI:10.1016/j.jsps.2012.01.005 · 1.00 Impact Factor
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    ABSTRACT: Novel betulinic acid derivative 5'-chloro-2, 3-didehydroindolo [2', 3': 2, 3] betulinic acid (DRF-4012) is a new effective lupane type triterpenes with greater anticancer activity and efficacy than betulinic acid and currently under advanced preclinical investigation phase. In this study, a sensitive and rapid liquid chromatography-electrospray mass spectrometric (LC/MS) method has been developed for the determination of DRF-4012 in tumour-bearing mice plasma, urine, feces and tissues (liver, brain, lungs, heart, spleen, stomach, thigh muscle, kidneys, urinary bladder, small intestine and tumour). Biodistribution and excretion studies were performed for DRF-4012 nanoparticle (30 mg/kg body weight) after intravenous (i.v.) injection in tumour-bearing mice. DRF-4012 rapidly distributed throughout the body. After 0.5 h, tumour showed the second highest concentration, which was nearly half of the liver. After 4 and 24 h, the highest concentration of DRF-4012 was found in tumour indicating its retention in tumour site for a longer time. Excretion studies revealed that very low amount of unchanged DRF-4012 was observed in urine and primarily excreted through fecal route. This study may be useful to explain the manner in which DRF-4012 can inhibit tumour growth without apparent toxicity and preclinical/clinical evaluation of this potential antitumour agent.
    Xenobiotica 12/2012; DOI:10.3109/00498254.2012.747709 · 2.10 Impact Factor
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    ABSTRACT: Development of an effective formulation involves careful optimization of a number of excipient and process variables. Sometimes the number of variables is so large that even the most efficient optimization designs require a very large number of trials which put stress on costs as well as time. A creative combination of a number of design methods leads to a smaller number of trials. This study was aimed at the development of nanostructured lipid carriers (NLCs) by using a combination of different optimization methods. A total of 11 variables were first screened using the Plackett-Burman design for their effects on formulation characteristics like size and entrapment efficiency. Four out of 11 variables were found to have insignificant effects on the formulation parameters and hence were screened out. Out of the remaining seven variables, four (concentration of tween-80, lecithin, sodium taurocholate, and total lipid) were found to have significant effects on the size of the particles while the other three (phase ratio, drug to lipid ratio, and sonication time) had a higher influence on the entrapment efficiency. The first four variables were optimized for their effect on size using the Taguchi L9 orthogonal array. The optimized values of the surfactants and lipids were kept constant for the next stage, where the sonication time, phase ratio, and drug:lipid ratio were varied using the Box-Behnken design response surface method to optimize the entrapment efficiency. Finally, by performing only 38 trials, we have optimized 11 variables for the development of NLCs with a size of 143.52 ± 1.2 nm, zeta potential of -32.6 ± 0.54 mV, and 98.22 ± 2.06% entrapment efficiency.
    Nanotechnology 12/2012; 24(1):015104. DOI:10.1088/0957-4484/24/1/015104 · 3.67 Impact Factor
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    ABSTRACT: CD44 or hyaluronan receptor is a transmembrane receptor associated with aggressive tumour growth, proliferation, and metastasis. In normal physiology, this receptor has a crucial role in cell adhesion, inflammation, and repair processes. However, many tumour cells over-express this receptor and abuse it to become progressive and perpetual units. The article comments from common functioning of the CD44 receptor, to its diabolic multi-dimensional effects in promotion of malignant cells. It also illuminates the relations of CD44 endorsed processes with other biomolecular events in cancer progression. In an end, the review focuses comprehensively at ongoing researches to exploit the CD44 over-expression as a probable target in treatment, management, and diagnosis of malignancy.
    Journal of Drug Targeting 08/2012; 20(7):561-73. DOI:10.3109/1061186X.2012.702767 · 2.72 Impact Factor
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    ABSTRACT: INTRODUCTION: An increasing research interest has been directed toward nanoparticle-based drug delivery systems for their advantages. The appropriate amalgamation of pH sensitivity and tumor targeting is a promising strategy to fabricate drug delivery systems with high efficiency, high selectivity and low toxicity. MATERIALS AND METHODS: A novel pH sensitive Cremophor-free paclitaxel formulation, Nanoxel(TM), was developed in which the drug is delivered as nanomicelles using a polymeric carrier that specifically targets tumors. The efficiency and mechanism of intracellular paclitaxel delivery by Nanoxel(TM) was compared with two other commercially available paclitaxel formulations: Abraxane(TM) and Intaxel(TM), using different cell lines representing target cancers [breast, ovary and non-small cell lung carcinoma (NSCLC)] by transmission electron microscopy and quantitative intracellular paclitaxel measurements by high performance liquid chromatography. RESULTS: The data obtained from the present study revealed that the uptake of nanoparticle-based formulations Nanoxel(TM) and Abraxane(TM) is mediated by the process of endocytosis and the uptake of paclitaxel was remarkably superior to Intaxel(TM) in all cell lines tested. Moreover, the intracellular uptake of paclitaxel in Nanoxel(TM)- and Abraxane(TM)-treated groups was comparable. Hence, the nanoparticle-based formulations of paclitaxel (Nanoxel(TM) and Abraxane(TM)) are endowed with higher efficiency to deliver the drug to target cells as compared to the conventional Cremophor-based formulation. CONCLUSION: Nanoxel(TM) appears to be of great promise in tumor targeting and may provide an advantage for paclitaxel delivery into cancer cells.
    Clinical and Translational Oncology 07/2012; 15(1). DOI:10.1007/s12094-012-0883-2 · 1.60 Impact Factor
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    ABSTRACT: In continuation with our previous work, structurally diverse 2-indolinones bearing 2,6-dichloroaryl fragment at N 1 and (hetero)aryl benzylidene at C3 were evaluated for their antitumor activity on a panel of cancer cell lines such as MCF-7 (breast), MiapaCa2 (pancreas), KB (oral), HuTu80 (stomach), L132 (lung), B16F10 (melanoma), and Molt4 (leukemia) from various human organs. Among the screened compound library, molecules 4e, 4k, and 4r have shown excellent cytotoxicity on a stomach cancer cell line. Moreover, a significant number of compounds have also shown promising cytotoxicity on pancreas and oral cancer cell lines.
    Medicinal Chemistry Research 07/2012; 22(7). DOI:10.1007/s00044-012-0309-2 · 1.61 Impact Factor
  • European Journal of Cancer 09/2011; 47. DOI:10.1016/S0959-8049(11)70830-9 · 4.82 Impact Factor

Publication Stats

582 Citations
148.75 Total Impact Points

Institutions

  • 2006–2014
    • Dabur Research Foundation
      Ghazibad, Uttar Pradesh, India
  • 2011
    • Jamia Hamdard University
      • Department of Pharmaceutics
      New Delhi, NCT, India
  • 2007
    • CSIR - National Chemical Laboratory, Pune
      Poona, Maharashtra, India
  • 2005
    • Indian Institute of Chemical Technology
      Bhaganagar, Andhra Pradesh, India