ARPIT BHARGAVA - Academia.edu (original) (raw)
Papers by ARPIT BHARGAVA
Asian Pacific Journal of Cancer Prevention Apjcp, 2011
Drug Delivery and Translational Research, 2015
Solid dispersion has emerged as a method of choice and has been extensively investigated to ascer... more Solid dispersion has emerged as a method of choice and has been extensively investigated to ascertain the in vivo improved performance of many drug formulations. It generally involves dispersion of drug in amorphous particles (clusters) or in crystalline particles. Comparatively, in the last decade, amorphous drug-polymer solid dispersion has evolved into a platform technology for delivering poorly water-soluble small molecules. However, the success of this technique in the pharmaceutical industry mainly relies on different drug-polymer attributes like physico-chemical stability, bioavailability and manufacturability. The present review showcases the efficacy of amorphous solid dispersion technique in the research and evolution of different drug formulations particularly for those with poor water soluble properties. Apart from the numerous mechanisms of action involved, a comprehensive summary of different key parameters required for the solubility enhancement and their translational efficacy to clinics is also emphasized.
International Journal of Occupational Medicine and Environmental Health, 2015
British Journal of Nutrition, 2011
Nutrition and Cancer, 2014
Journal of Global Infectious Diseases, 2011
International Journal of Toxicology, 2011
Indian Journal of Pathology and Microbiology, 2011
I n d I a n J o u r n a l o f P a t h o l o g y a n d M I c r o b I o l o g y -5 4 ( 2 ) , a P r ... more I n d I a n J o u r n a l o f P a t h o l o g y a n d M I c r o b I o l o g y -5 4 ( 2 ) , a P r I l -J u n e 2 0 1 1 408
Gastroenterology, 2009
Gastroenterology, Volume 136, Issue 5, Pages A-923, May 2009, Authors:Kewal K. Maudar; ArpitBharg... more Gastroenterology, Volume 136, Issue 5, Pages A-923, May 2009, Authors:Kewal K. Maudar; ArpitBhargava; Ram P. Punde; Subodh Varshney; Pradyumna K. Mishra. ... Kewal K. Maudar ,; ArpitBhargava ,; Ram P. Punde ,; Subodh Varshney ,; Pradyumna K. Mishra. Abstract; PDF. ...
Extra-pulmonary tuberculosis is often an underrated illness. Recent clinical studies have pointed... more Extra-pulmonary tuberculosis is often an underrated illness. Recent clinical studies have pointed out that lymphocyte
homeostasis is dramatically disturbed as revealed through a series of signs and symptoms. Lymphocytes, the known effector
cells of our immune system, play an important role in providing immunologic resistance against Mycobacterium infection. It is
important to have quantitative insights into the lifespan of these cells; therefore, we aimed to study the precise effect of
gastrointestinal tuberculosis infection on peripheral blood lymphocyte subpopulations and function. Our results indicated
that gastrointestinal tuberculosis could increase mitochondrial oxidative stress, lower mitochondrial DNA copy number,
promote nuclear DNA damage and repair response, decrease mitochondrial respiratory chain enzyme activities, and
upregulate Bcl-2 and caspase-3 gene expression in lymphocytes. We further revealed that Mycobacterium infection induces
autophagy for selective sequestration and subsequent degradation of the dysfunctional mitochondrion before activating
cellular apoptosis in the peripheral lymphocyte pool. Together, these observations uncover a new role of mitochondrial–
nuclear crosstalk that apparently contributes to lymphocyte homeostasis in gastrointestinal tuberculosis infection.
Indian journal of community medicine : official publication of Indian Association of Preventive & Social Medicine, 2014
Nanomedicine, 2013
The work attempts to overcome tumor-associated immune tolerance using a surface-modified solid li... more The work attempts to overcome tumor-associated immune tolerance using a surface-modified solid lipid nanoparticle (SLNP) delivery system for dendritic cell (DC) immunotherapy. Different formulations of SLNPs (SLNPs-alone, cationic SLNPs and mannosylated SLNPs) were prepared using tumor cell lysates. Prepared nanoparticles were characterized and their ability to activate DCs to induce a tumor cell-specific response was assessed. SLNPs induced a strong phagocytic signal to DCs without any significant toxicity. Comparatively, mannosylated SLNPs evoked an optimum and effective cell-mediated immune response with no significant toxicity. Surface-modified SLNPs may play a pivotal role in designing a clinically translatable DC-based immunotherapy for gastrointestinal malignancies. This novel approach may also facilitate the treatment of residual disease, following standard therapy.
Immunotherapy, 2012
Dendritic cells (DCs) are the most potent APCs, with the ability to orchestrate a repertoire of i... more Dendritic cells (DCs) are the most potent APCs, with the ability to orchestrate a repertoire of immune responses. DCs play a pivotal role in the initiation, programming and regulation of tumor-specific immune responses, as they are poised to take up, process and present tumor antigens to naive or effector T lymphocytes. Although, to an extent, DC-based immunotherapeutic strategies have successfully induced specific anti-tumor responses in animal models, their clinical efficacy has rarely been translated into the clinic. This article attempts to present a complete picture of recent developments of DC-based therapeutic strategies addressing multiple components of tumor immunoenvironment. It also showcases certain practical intricacies in order to explore novel strategies for providing new impetus to DC-based cancer vaccination.
Journal of Drug Targeting, 2013
Gastrointestinal (GI) malignancies are one of the most frequently occurring tumors found worldwid... more Gastrointestinal (GI) malignancies are one of the most frequently occurring tumors found worldwide. Surgery remains the primary treatment for most solid tumors and adjuvant chemotherapy and radiotherapy are limited by lack of specificity and toxicity. In view of the poor survival rate, there is a great need to introduce new and effective therapeutic modalities. Recently, dendritic cells (DCs)-based vaccines are being explored as a promising therapeutic strategy but their success is limited by the tumor-induced immune escape mechanisms. This article provides a comprehensive analysis of clinical trials conducted using this approach. It also showcases the necessity of exploring nano-engineered strategies for improving the clinical utility of DC-vaccination for GI tract malignancies to overcome immune tolerance.
Nanomedicine, 2014
Nanomedicine may play an important role in improving the clinical efficacy of dendritic cell-base... more Nanomedicine may play an important role in improving the clinical efficacy of dendritic cell-based immunotherapy against GI tract malignancies. Dendritic cell-based vaccines have proven their effectiveness against different established GI tract tumors, yet their success is mainly hindered by the strong tumor-induced suppressive microenvironment. The sustained and targeted release of tumor antigens to dendritic cells using different nanoengineered approaches would be an efficient strategy to overcome established immune tolerance. Encapsulation would result in low diffusivity, restricted movement, effective crosspresentation and enhanced T-cell responses. These nanotherapy-based approaches will certainly help with the designing of clinically translatable dendritic cell-based therapeutic vaccines and facilitate the selective removal of residual disease in gastrointestinal cancer patients following standard treatments.
Reproductive Toxicology, 2015
The present work reports a direct role of mitochondrial oxidative stress induced aberrant chromat... more The present work reports a direct role of mitochondrial oxidative stress induced aberrant chromatin regulation, as a central phenomenon, to perturbed genomic integrity in the testicular milieu. Oxygen-radical injury following N-succinimidyl N-methylcarbamate treatment in mouse spermatogonial epithelial (GC-1 spg) cells induced functional derailment of mitochondrial machinery. Mitophagy resulted in marked inhibition of mitochondrial respiration and reduced mtDNA copy number. Impaired cell cycle progression along with altered H3K9me1, H4K20me3, H3, AcH3 and uH2A histone modifications were observed in the treated cells. Dense heterochromatin foci and aberrant expression of HP1α in nuclei of treated cells implied onset of senescence associated secretory phenotype mediated through nuclear accumulation of NF-κB. Neoplastic nature of daughter clones, emerged from senescent mother phenotypes was confirmed by cytogenetic instability, aberrant let-7a and let-7b miRNA expression and anchorage independent growth. Together, our results provide the first insights of redox-dependent epigenomic imbalance in spermatogonia, a previously unknown molecular paradigm.
Asian Pacific Journal of Cancer Prevention Apjcp, 2011
Drug Delivery and Translational Research, 2015
Solid dispersion has emerged as a method of choice and has been extensively investigated to ascer... more Solid dispersion has emerged as a method of choice and has been extensively investigated to ascertain the in vivo improved performance of many drug formulations. It generally involves dispersion of drug in amorphous particles (clusters) or in crystalline particles. Comparatively, in the last decade, amorphous drug-polymer solid dispersion has evolved into a platform technology for delivering poorly water-soluble small molecules. However, the success of this technique in the pharmaceutical industry mainly relies on different drug-polymer attributes like physico-chemical stability, bioavailability and manufacturability. The present review showcases the efficacy of amorphous solid dispersion technique in the research and evolution of different drug formulations particularly for those with poor water soluble properties. Apart from the numerous mechanisms of action involved, a comprehensive summary of different key parameters required for the solubility enhancement and their translational efficacy to clinics is also emphasized.
International Journal of Occupational Medicine and Environmental Health, 2015
British Journal of Nutrition, 2011
Nutrition and Cancer, 2014
Journal of Global Infectious Diseases, 2011
International Journal of Toxicology, 2011
Indian Journal of Pathology and Microbiology, 2011
I n d I a n J o u r n a l o f P a t h o l o g y a n d M I c r o b I o l o g y -5 4 ( 2 ) , a P r ... more I n d I a n J o u r n a l o f P a t h o l o g y a n d M I c r o b I o l o g y -5 4 ( 2 ) , a P r I l -J u n e 2 0 1 1 408
Gastroenterology, 2009
Gastroenterology, Volume 136, Issue 5, Pages A-923, May 2009, Authors:Kewal K. Maudar; ArpitBharg... more Gastroenterology, Volume 136, Issue 5, Pages A-923, May 2009, Authors:Kewal K. Maudar; ArpitBhargava; Ram P. Punde; Subodh Varshney; Pradyumna K. Mishra. ... Kewal K. Maudar ,; ArpitBhargava ,; Ram P. Punde ,; Subodh Varshney ,; Pradyumna K. Mishra. Abstract; PDF. ...
Extra-pulmonary tuberculosis is often an underrated illness. Recent clinical studies have pointed... more Extra-pulmonary tuberculosis is often an underrated illness. Recent clinical studies have pointed out that lymphocyte
homeostasis is dramatically disturbed as revealed through a series of signs and symptoms. Lymphocytes, the known effector
cells of our immune system, play an important role in providing immunologic resistance against Mycobacterium infection. It is
important to have quantitative insights into the lifespan of these cells; therefore, we aimed to study the precise effect of
gastrointestinal tuberculosis infection on peripheral blood lymphocyte subpopulations and function. Our results indicated
that gastrointestinal tuberculosis could increase mitochondrial oxidative stress, lower mitochondrial DNA copy number,
promote nuclear DNA damage and repair response, decrease mitochondrial respiratory chain enzyme activities, and
upregulate Bcl-2 and caspase-3 gene expression in lymphocytes. We further revealed that Mycobacterium infection induces
autophagy for selective sequestration and subsequent degradation of the dysfunctional mitochondrion before activating
cellular apoptosis in the peripheral lymphocyte pool. Together, these observations uncover a new role of mitochondrial–
nuclear crosstalk that apparently contributes to lymphocyte homeostasis in gastrointestinal tuberculosis infection.
Indian journal of community medicine : official publication of Indian Association of Preventive & Social Medicine, 2014
Nanomedicine, 2013
The work attempts to overcome tumor-associated immune tolerance using a surface-modified solid li... more The work attempts to overcome tumor-associated immune tolerance using a surface-modified solid lipid nanoparticle (SLNP) delivery system for dendritic cell (DC) immunotherapy. Different formulations of SLNPs (SLNPs-alone, cationic SLNPs and mannosylated SLNPs) were prepared using tumor cell lysates. Prepared nanoparticles were characterized and their ability to activate DCs to induce a tumor cell-specific response was assessed. SLNPs induced a strong phagocytic signal to DCs without any significant toxicity. Comparatively, mannosylated SLNPs evoked an optimum and effective cell-mediated immune response with no significant toxicity. Surface-modified SLNPs may play a pivotal role in designing a clinically translatable DC-based immunotherapy for gastrointestinal malignancies. This novel approach may also facilitate the treatment of residual disease, following standard therapy.
Immunotherapy, 2012
Dendritic cells (DCs) are the most potent APCs, with the ability to orchestrate a repertoire of i... more Dendritic cells (DCs) are the most potent APCs, with the ability to orchestrate a repertoire of immune responses. DCs play a pivotal role in the initiation, programming and regulation of tumor-specific immune responses, as they are poised to take up, process and present tumor antigens to naive or effector T lymphocytes. Although, to an extent, DC-based immunotherapeutic strategies have successfully induced specific anti-tumor responses in animal models, their clinical efficacy has rarely been translated into the clinic. This article attempts to present a complete picture of recent developments of DC-based therapeutic strategies addressing multiple components of tumor immunoenvironment. It also showcases certain practical intricacies in order to explore novel strategies for providing new impetus to DC-based cancer vaccination.
Journal of Drug Targeting, 2013
Gastrointestinal (GI) malignancies are one of the most frequently occurring tumors found worldwid... more Gastrointestinal (GI) malignancies are one of the most frequently occurring tumors found worldwide. Surgery remains the primary treatment for most solid tumors and adjuvant chemotherapy and radiotherapy are limited by lack of specificity and toxicity. In view of the poor survival rate, there is a great need to introduce new and effective therapeutic modalities. Recently, dendritic cells (DCs)-based vaccines are being explored as a promising therapeutic strategy but their success is limited by the tumor-induced immune escape mechanisms. This article provides a comprehensive analysis of clinical trials conducted using this approach. It also showcases the necessity of exploring nano-engineered strategies for improving the clinical utility of DC-vaccination for GI tract malignancies to overcome immune tolerance.
Nanomedicine, 2014
Nanomedicine may play an important role in improving the clinical efficacy of dendritic cell-base... more Nanomedicine may play an important role in improving the clinical efficacy of dendritic cell-based immunotherapy against GI tract malignancies. Dendritic cell-based vaccines have proven their effectiveness against different established GI tract tumors, yet their success is mainly hindered by the strong tumor-induced suppressive microenvironment. The sustained and targeted release of tumor antigens to dendritic cells using different nanoengineered approaches would be an efficient strategy to overcome established immune tolerance. Encapsulation would result in low diffusivity, restricted movement, effective crosspresentation and enhanced T-cell responses. These nanotherapy-based approaches will certainly help with the designing of clinically translatable dendritic cell-based therapeutic vaccines and facilitate the selective removal of residual disease in gastrointestinal cancer patients following standard treatments.
Reproductive Toxicology, 2015
The present work reports a direct role of mitochondrial oxidative stress induced aberrant chromat... more The present work reports a direct role of mitochondrial oxidative stress induced aberrant chromatin regulation, as a central phenomenon, to perturbed genomic integrity in the testicular milieu. Oxygen-radical injury following N-succinimidyl N-methylcarbamate treatment in mouse spermatogonial epithelial (GC-1 spg) cells induced functional derailment of mitochondrial machinery. Mitophagy resulted in marked inhibition of mitochondrial respiration and reduced mtDNA copy number. Impaired cell cycle progression along with altered H3K9me1, H4K20me3, H3, AcH3 and uH2A histone modifications were observed in the treated cells. Dense heterochromatin foci and aberrant expression of HP1α in nuclei of treated cells implied onset of senescence associated secretory phenotype mediated through nuclear accumulation of NF-κB. Neoplastic nature of daughter clones, emerged from senescent mother phenotypes was confirmed by cytogenetic instability, aberrant let-7a and let-7b miRNA expression and anchorage independent growth. Together, our results provide the first insights of redox-dependent epigenomic imbalance in spermatogonia, a previously unknown molecular paradigm.