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Dive into the research topics where Amit Tyagi is active.

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Featured researches published by Amit Tyagi.


European Journal of Pharmaceutical Sciences | 2017

“Gold nanoparticles composite-folic acid conjugated graphene oxide nanohybrids” for targeted chemo-thermal cancer ablation: In vitro screening and in vivo studies

Gaurav Chauhan; Vianni Chopra; Amit Tyagi; Goutam Rath; Rakesh Kumar Sharma; Amit K. Goyal

&NA; Nano‐graphene oxide (GO) nanometal composite (specifically nanogold and nanosilver) have shown to be a promising material for anticancer therapeutics. Owing to their high drug loading capacity, photothermal and synergizing effects, it is very important to exploit them for targeted chemo‐thermal cancer therapeutics. In this work, gold nanoparticles (AuNPs) were selected as the composite metal, folic acid (FA) was taken as GO surface functionalization moiety for active tumor targeting of model anticancer drug Doxorubicin (Dox). AuNPs composite‐folate conjugated graphene oxide (FA‐GO@Au) nano‐platforms were synthesized and characterized in detail. Near‐infrared (NIR) sensitivity resulted in an aggravated release of both Dox and ionic gold from the nanohybrid surface. Simultaneous delivery of Dox and AuNPs in the cellular vicinity was further enhanced after localized NIR exposure which resulted in significantly improved cancer cell toxicity. Mechanistic evaluation revealed G0/G1 phase arrest due to increased DNA intercalation and provoked early apoptosis under NIR influence. Pharmacokinetics and organ distribution studies were carried out in healthy mice and rabbits to estimate the actual bio fate of these nanohybrids. In vivo studies showed substantial tumor regression in solid tumor model in Balb/c mice and NIR exposure induced photo‐thermal effects further resulted in better tumor management. Study provides substantial evidences both at in vitro and in vivo level to support the fact that NIR induced local photo‐thermal effects can solely be used as a tumor targeting tool. This NIR dependent nanohybrid approach presents a precise and flexible strategy for targeted chemotherapy and photo‐thermal tumor ablation. Graphical abstract Figure. No caption available.


Drug Delivery | 2016

A gamma scintigraphy study to investigate uterine targeting efficiency of raloxifene-loaded liposomes administered intravaginally in New Zealand white female rabbits

Arpita Patel; Amit Tyagi; Rakesh Kumar Sharma; Hetal Thakkar

Abstract Context: Raloxifene hydrochloride (RLH), a selective estrogen receptor modulator, shows antiproliferative and apoptotic effects on Leiomyoma. Its extensive first pass metabolism leads to oral bioavailability of 2%. Objective: The aim of this investigation was to formulate RLH-loaded liposomes and study its uterine-targeting efficiency after intravaginal administration. Materials and methods: Liposomes were prepared by thin film hydration method using 1:1 molar ratio of DSPC:Cholesterol and characterized for vesicle size, zeta potential, %entrapment efficiency, loading, drug release and transmission electron microscopy. Radiolabeling of RLH was performed with reduced technetium-99m (99mTc). Binding affinity of 99mTc-labeled complexes was assessed by diethylene triamine penta acetic acid (DTPA) challenge test. Biodistribution study was done in New Zealand white female rabbits by administering the formulation intravaginally. Results and discussion: Spherical and discrete liposomes of size 119 nm were seen in TEM results. Liposomes had high entrapment efficiency of 90.96% with drug loading of 27.25%w/w. Liposomes were able to sustain the drug release for 6 days. 99mTc-labeled complexes showed high labeling efficiency and stability both in saline and serum. DTPA challenge test confirmed low transchelation of 99mTc-labeled complexes. Biodistribution study by gamma scintigraphy revealed the preferential uptake of the formulation by uterus when administered vaginally. Compared to plain drug, liposomes were concentrated and retained within the uterus for a longer period of time. Conclusion: Uterine targeting of RLH-loaded liposomes indicates its potential to overcome the limitations of marketed formulation. Drug targeting to site of action anticipates dose reduction needed to elicit the therapeutic effect.


Archivos De Bronconeumologia | 2015

El factor de crecimiento queratinocítico humano recombinante induce la progresión de la supervivencia celular mediada por Akt en ratones enfisematosos

Jai Prakash Muyal; Dhananjay Kumar; Sudhir Kotnala; Vandana Muyal; Amit Tyagi

INTRODUCTION Emphysema has been associated with decreased VEGF and VEGFR-2 expression and the presence of high numbers of apoptotic alveolar cells. Keratinocyte growth factor stimulates VEGF synthesis which in turn confers normal lung structure maintenance via the Akt pathway. In this study the potential role of rHuKGF in the improvement of deregulated Akt mediated cell survival pathway in emphysematous mice was investigated. METHODS Three experimental groups, i.e., emphysema, treatment and control groups, were prepared. Lungs of mice were treated on 3 occasions by oropharyngeal instillation of 10mg rHuKGF per kg body weight after induction of emphysema with porcine pancreatic elastase. Subsequently, lung tissues from mice were collected for histopathology and molecular biology studies. RESULTS AND DISCUSSION Histopathology photomicrographs and destructive index analysis have shown that elastase-induced airspace enlargement and loss of alveoli recovered in the treatment group. rHuKGF stimulates VEGF production which in turn induces the Akt mediated cell survival pathway in emphysematous lungs. mRNA expression of VEGF, VEGFR, PI3K and Akt was significantly increased while Pten, Caspase-9 and Bad was notably decreased in treatment group when compared with emphysema group, being comparable with the control group. Moreover, VEGF protein expression was in accordance with that found for mRNA. CONCLUSION Therapeutic rHuKGF supplementation improves the deregulated Akt pathway in emphysema, resulting in alveolar cell survival through activation of the endogenous VEGF-dependent cell survival pathway. Hence rHuKGF may prove to be a potential drug in the treatment of emphysema.


Inhalation Toxicology | 2014

Effect of recombinant human keratinocyte growth factor in inducing Ras–Raf–Erk pathway-mediated cell proliferation in emphysematous mice lung

Jai Prakash Muyal; Sudhir Kotnala; Harsh Bhardwaj; Amit Tyagi

Abstract Context: Pulmonary emphysema is resulted due to destruction of the structure of the alveoli. Recently, exogenous recombinant human Keratinocyte growth factor (rHuKGF) has been reported to induce the regeneration of gas exchange structures. However, the molecular mechanisms governing this process are so far unknown. Objective: The objective of this study was to investigate the effect of rHuKGF in the lungs of emphysema-challenged mice on Ras–Raf–Erk (Erk, extracellular signal-regulated kinase) mediated signaling pathway that regulates alveolar epithelial cell proliferation. Methods: Three experimental groups (i.e. emphysema, therapy and control group) were prepared. Lungs of mice were therapeutically treated at three occasions by oropharyngeal instillation of 10 mg rHuKGF per kg body weight after induction of emphysema by porcine pancreatic elastase (PPE). Subsequently, lung tissues from each mouse were collected for histopathology and molecular biology studies. Results and discussion: Histopathology photomicrographs and Destructive Index analysis have shown that elastase induced airspace enlargement and loss of alveoli were recovered in therapy group. Moreover, proliferating cell nuclear antigen (PCNA) at mRNA and protein expression level was markedly increased in therapy group than emphysema group. Upon validation at mRNA level, expressions of FGF-7, FGF-R, Ras, c-Raf, Erk-1, Erk-2, c-Myc and were significantly increased, whereas Elk-1 was notably decreased in therapy group when compared with emphysema group and were well comparable with the control group. Conclusion: Therapeutic supplementation of rHuKGF rectifies the deregulated Ras–Raf–Erk pathway in emphysema condition, resulting in alveolar epithelium regeneration. Hence, rHuKGF may prove to be a potential drug in the treatment of emphysema.


Inhalation Toxicology | 2017

Recombinant human keratinocyte growth factor attenuates apoptosis in elastase induced emphysematous mice lungs

Sudhir Kotnala; Sumit Baghel; Deepali Verma; Amit Tyagi; Jai Prakash Muyal

Abstract Alveolar cell apoptosis is one of the potential factors involved in the pathogenesis of emphysema. Recently, exogenous recombinant human keratinocyte growth factor (rHuKGF) has been reported to induce the regeneration of gas exchange structures. Therefore, the rationale of the present study was to investigate the potential effect of rHuKGF in ameliorating tissue destruction in the emphysematous mice lungs. Four experimental groups (i.e. control-, emphysema-, therapy- and therapy control-group) were prepared. Subsequently, lungs from each mouse were collected for comet assay, elastase activity assay, antioxidant activity assay and real-time PCR based analyses. Comet assay analysis demonstrated the reduced tail DNA % and olive tail moment in therapy group. rHuKGF supplementation in emphysematous mice caused a significant reduction in the elastase activity levels along with reduction in activity of CAT, SOD and GPx. Furthermore, based on mRNA expression studies, the supplementation of rHuKGF ameliorated the induced apoptosis pathway in emphysematous mice lungs. Moreover, due to rHuKGF supplementation, TNF-α and p53 expression and production were markedly decreased in emphysematous mice lungs. Thus, therapeutic supplementation of rHuKGF might have reversed the alveolar cell loss in elastase induced emphysematous mice lungs by reducing DNA damage and maintaining antioxidant activities.


Anesthesia: Essays and Researches | 2016

Influence of two anesthetic techniques on blood sugar level in head injury patients: A comparative study

Manoj Kumar; Manoj Tripathi; Deepak Malviya; Ps Malviya; Virendra Kumar; Amit Tyagi

Background: Head injury presents a major worldwide social, economic, and health problem. Hyperglycemia is a significant indicator of the severity of injury and predictor of outcome, which can easily be prevented. There has been a long-standing controversy regarding the use of inhalational or intravenous (i.v.) anesthetic agents for surgery of head injury cases and impact of these agents on blood sugar level. Aims and Objectives: The aim of this study is to find out anesthetic drugs and technique having minimal or no effect on the blood sugar, and Glasgow Coma Scale (GCS) of patients with a head injury by comparing two types of anesthetic techniques in surgery of head injury patients. Materials and Methods: This was a prospective, randomized, and comparative study, conducted on 60 adult head injury patients. The patients were divided into two groups of 30 each. Group I patients received induction with sevoflurane and then had O2 + air + sevoflurane for maintenance with controlled ventilation. Group II patients received induction with i.v. propofol and then had O2 + air + propofol for maintenance with controlled ventilation. Injection fentanyl was used in both the groups at the time of induction and in intermittent boluses in maintenance. In observation, blood sugar level and mean arterial pressure were assessed at different time periods perioperatively in both groups while GCS was analyzed pre- and post-operatively. Statistical Analysis: Statistical analysis was performed by Microsoft Excel 2010 using t-test for comparison between the two groups and Z-test for comparison of proportions. Results and Conclusion: Blood sugar level was found significantly higher in patients of sevoflurane group at 30 min after induction, at the end of surgery, and 1 h after the end of anesthesia than propofol group patients. This increase of blood sugar level did not have any significant alteration in the GCS profile of the patients in sevoflurane group as compared to propofol group patients. Nausea and vomiting were found more in sevoflurane group while hypotension and bradycardia were found more with propofol group.


Rejuvenation Research | 2018

Baclofen-Loaded Poly (d,l-Lactide-Co-Glycolic Acid) Nanoparticles for Neuropathic Pain Management: In Vitro and In Vivo Evaluation

Kuldeep Nigam; Atinderpal Kaur; Amit Tyagi; Kailash Manda; Reema Gabrani; Shweta Dang

In this work, poly (D,L-lactide-co-glycolic acid) (PLGA) nanoparticles of baclofen (Bcf-PLGA-NPs) were developed and optimized using nanoprecipitation method. The average particle size of the Bcf-PLGA-NP was found to be 124.8 nm, polydispersity index of 0.225, and zeta potential was found to be in the range of -20.4 mV. In vitro dissolution studies showed that Bcf was released from PLGA NPs in a sustained manner from 50% release in 2.5 hours to 80%-85% in 24 hours. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay on Neuro-2a neuroblastoma cell line showed comparably low cytotoxicity of Bcf-PLGA-NPs as compared with aqueous solution of Bcf at reported Cmax values of the drug. To explore the nose-to-brain pathway, in vivo studies were carried out in Sprague-Dawley rats by radiolabeling of Bcf with technetium-99m (99mTc). Gamma scintigraphy images of the rats that were administered through intranasal (i.n.) route showed the maximum uptake of radiolabeled NPs from nose to brain at 3 hours as compared with the rats administered with NPs intravenously and orally. To assess the Bcf concentration in brain and blood, biodistribution studies were performed and following i.n. route the NPs were dispersed in brain (3.5%/g) and blood (3%/g) at 3 hours, and these observations were in agreement with the gamma scintigrams. Hence, from the results it was suggested that the developed PLGA NPs could serve as a potential carrier for the Bcf in the treatment of neuropathic pain.


Pulmonary Pharmacology & Therapeutics | 2018

99m Tc-vinorelbine tartrate loaded spherulites: Lung disposition study in Sprague-Dawley rats by gamma scintigraphy

Rahul Dhande; Amit Tyagi; Rakesh Kumar Sharma; Hetal Thakkar

Vinorelbine Tartrate (VLB) is the first line chemotherapeutic agent for treatment of Non-Small Cell Lung Cancer, whose non-specific distribution causes unwanted side effects. The aim of the present investigation was to formulate VLB loaded spherulites intended for targeting the lung. Spherulites were composed of Soyabean Phosphatidylcholine (SPC), Cholesterol (Chol), Potassium oleate and Mannitol. Lipid film prepared using SPC, Chol and Potassium oleate, was dispersed in aqueous phase comprising Mannitol and VLB, followed by controlled shearing and extrusion. PEGylated Spherulites were prepared by incorporating 1,2-distearoyl-sn-glycero-3 phosphatidylethanolamine-N-[methoxy poly (ethylene glycol)] (DSPE-PEG 2000) in the lipid phase. Vesicles were characterized for size, entrapment efficiency and drug release. In vitro cell cytotoxicity and apoptosis study were performed on A549 cell line. Radiolabeling of VLB was performed by direct labeling with reduced technetium-99m. Binding affinity of 99mTc- labelled complexes was assessed by diethylenetriaminepenta acetic acid (DTPA) challenge test. Biodistribution study was done in Sprague Dawley rats. Dynamic light scattering and Transmission electron micrographs confirmed that PEGylated and non-PEGylated Spherulites were discrete, spherical and exhibited the size range of 120-130 nm. Non-PEGylated and PEGylated Spherulites had an entrapment efficiency of 95.65% and 94.2% respectively. In vitro drug release study indicated VLB plain drug solution diffused completely within 24 h, however, Non-PEGylated and PEGylated Spherulites showed similar release pattern till 48 h. Results of cell line study showed that cells treated with VLB loaded Spherulites showed more cytotoxicity and underwent high degree of apoptosis at lower concentration compared to the VLB solution. Radiolabeled complex was stable in saline and serum, further, DTPA challenge study ensured the high binding strength. Gamma Scintigraphy displayed that PEGylated Spherulites were localized within lungs at higher concentration than non-PEGylated followed by plain drug.


Nanomedicine: Nanotechnology, Biology and Medicine | 2018

Concomitant Delivery of Paclitaxel and NuBCP-9 peptide for synergistic enhancement of cancer therapy

Dikshi Gupta; Manoj Kumar; Priyanka Tyagi; Sumeet Kapoor; Amit Tyagi; Tarani Kanta Barman; Surender Kharbanda; Donald Kufe; Harpal Singh

Paclitaxel (PTX) is a microtubule inhibitor administered as an albumin-bound nanoformulation for the treatment of breast cancer. However, the effectiveness of PTX is limited by resistance mechanisms mediated in part by upregulation of the anti-apoptotic BCL-2 and P-glycoprotein (P-gp). Present investigation was designed to study the synergistic potential of NuBCP-9 and PTX loaded polymeric nanoparticles to minimize the dose and improve the efficacy and safety. PTX and NuBCP-9 loaded polylactic acid-polyethylene glycol-polypropylene glycol-polyethylene glycol [PLA-(PEG-PPG-PEG)] nanoparticles were prepared by double emulsion solvent evaporation method. PTX and NuBCP-9 loaded NPs displayed an average size of 90 nm with spherical morphology. PTX and NuBCP-9 dual loaded NPs reducedIC50 by ~40-fold and acted synergistically. Treatment of the syngeneic EAT mice with PTX-NuBCP-9/NPs resulted in improved efficacy than that alone treated mice. Overall, the concomitant delivery PTX and NuBCP-9 loaded NPs showed superior activity than that of PTX and NuBCP-9 alone treated mice.


Biomedicine & Pharmacotherapy | 2018

ATRA reduces inflammation and improves alveolar epithelium regeneration in emphysematous rat lung

Swati Uniyal; Anupam Dhasmana; Amit Tyagi; Jai Prakash Muyal

INTRODUCTION Pulmonary emphysema characterized by alveolar wall destruction is resultant of persistent chronic inflammation. All-trans retinoic acid (ATRA) has been reported to reverse elastase-induced emphysema in rats. However, the underlying molecular mechanisms are so far unknown. OBJECTIVE To investigate the therapeutic potential effect of ATRA via the amelioration of the ERK/JAK-STAT pathways in the lungs of emphysematous rats. METHODS In silico analysis was done to find the binding efficiency of ATRA with receptor and ligands of ERK & JAK-STAT pathway. Emphysema was induced by porcine pancreatic elastase in Sprague-Dawley rats and ATRA was supplemented as therapy. Lungs were harvested for histopathological, genomics and proteomics analysis. RESULTS AND DISCUSSION In silico docking, analysis confirms that ATRA interferes with the normal binding of ligands (TNF-α, IL6ST) and receptors (TNFR1, IL6) of ERK/JAK-STAT pathways respectively. ATRA restored the histology, proteases/antiproteases balance, levels of inflammatory markers, antioxidants, expression of candidate genes of ERK and JAK-STAT pathways in the therapy group. CONCLUSION ATRA ameliorates ERK/JAK-STAT pathway in emphysema condition, resulting in alveolar epithelium regeneration. Hence, ATRA may prove to be a potential drug in the treatment of emphysema.

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Sudhir Kotnala

Gautam Buddha University

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Hetal Thakkar

Maharaja Sayajirao University of Baroda

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Atinderpal Kaur

Jaypee Institute of Information Technology

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Manoj Kumar

Indian Institute of Technology Delhi

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Reema Gabrani

Jaypee Institute of Information Technology

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Shweta Dang

Jaypee Institute of Information Technology

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Arpita Patel

Maharaja Sayajirao University of Baroda

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