advait shetty - Academia.edu (original) (raw)

Papers by advait shetty

bioRxiv (Cold Spring Harbor Laboratory), Mar 4, 2024

INDIAN DRUGS, 2015

Microfabrication is a collection of techniques developed to fabricate micron sized features, best... more Microfabrication is a collection of techniques developed to fabricate micron sized features, best suited to develop the novel drug delivery microdevices. microfabrication techniques were originally developed in the microelectronics industry to produce functional devices on the micron scale such as sensors, switches, filters and gears. Approaches like modification of drug itself to improve its permeability/ solubility characters, encapsulation techniques using micro/nanoparticles, use of protease inhibitors to curb proteolytic degradation, and use of intelligent polymers and hydrogels do not offer a complete solution for adequate and safe delivery of drugs, vaccines, peptides, proteins and others. This technology has been applied to the successful fabrication of a variety of implantable and oral drug delivery devices based on silicon, glass, silicone elastomer or plastic materials. These techniques that are utilized at present have developed as a result of integrated circuit manufact...

Microbiology Spectrum

Analysis of venereal transmission of Leptospira is important to determine if direct animal to ani... more Analysis of venereal transmission of Leptospira is important to determine if direct animal to animal transmission occurs, which could impact measures to prevent and treat leptospirosis. The goal of this study was to determine if live Leptospira colonize mouse testes.

Frontiers in Immunology, 2022

Leptospirosis is an emerging infectious disease. Recently, canine and human leptospirosis outbrea... more Leptospirosis is an emerging infectious disease. Recently, canine and human leptospirosis outbreaks were reported in California and New York, respectively. In this study we evaluated the role that cell death processes play in the inflammatory response to Leptospira. Groups of male C3H/HeJ mice were infected with pathogenic L. interrogans and non-pathogenic L. biflexa for 24 and 72 hours; inflammatory processes were characterized for apoptosis and necroptosis by flowcytometry of spleen cells and were further assessed for expression of biomarkers of necroptosis by western blot. We found that pathogenic L. interrogans promotes apoptosis in myeloid neutrophils and monocytes at 24h and 72h post-infection, whereas L. biflexa promotes apoptosis of myeloid monocytes only at 24h post-infection. It is interesting that the immune cells undergoing the common programmed cell death pathway (apoptosis) are the cell types which were not increased in frequency in spleen of mice infected with L. inte...

PLOS Neglected Tropical Diseases, 2022

The laborious microscopic agglutination test (MAT) is the gold standard serologic test for labora... more The laborious microscopic agglutination test (MAT) is the gold standard serologic test for laboratory diagnosis of leptospirosis. We developed EIA based serologic assays using recombinant proteins (rLigA, rLigB, rLipL32) and whole-cell extracts from eight Leptospira serovars as antigen and assessed the diagnostic performance of the new assay within each class, against MAT positive (MAT+) human sera panels from Portugal/PT (n = 143) and Angola/AO (n = 100). We found that a combination of recombinant proteins rLigA, rLigB and rLipL32 correctly identified antigen-specific IgG from patients with clinical and laboratory confirmed leptospirosis (MAT+) with 92% sensitivity and ~ 97% specificity (AUC 0.974) in serum from the provinces of Luanda (LDA) and Huambo (HBO) in Angola. A combination of whole cell extracts of L. interrogans sv Copenhageni (LiC), L. kirschneri Mozdok (LkM), L. borgpetersenii Arborea (LbA) and L. biflexa Patoc (LbP) accurately identified patients with clinical and lab...

Pharmaceutics, 2020

Pancreatic cancer (PanCa) is a lethal disease. Conventional chemotherapies for PanCa offer severe... more Pancreatic cancer (PanCa) is a lethal disease. Conventional chemotherapies for PanCa offer severe systemic toxicities. Thus, the development of a successful nanomedicine-based therapeutic regimen with augmented therapeutic efficacy is highly sought. Naturally occurring pectin and modified pectin-based drug delivery systems exhibit remarkable self-targeting ability via galactose residues to various cancer cells. Herein, we developed and used an innovative approach of highly stable nanocomplexes based on modified pectin and tannic acid (MPT-NCs). The nanocomplex formation was enabled by strong intermolecular interactions between pectin and tannic acid under very mild conditions. These nanocomplexes were characterized by particle size and morphology (DLS, TEM, and SEM), FT-IR spectroscopy, and zeta potential measurements. Additionally, MPT-NCs were capable of encapsulating anticancer drugs (5-fluorouracil, gemcitabine, and irinotecan) through tannic acid binding. The in vitro bioactivi...

ACS Omega, 2020

Pancreatic cancer (PanCa) is a highly lethal disease with a poor 5 year survival rate, less than ... more Pancreatic cancer (PanCa) is a highly lethal disease with a poor 5 year survival rate, less than 7%. It has a dismal prognosis, and more than 50% of cases are detected at an advanced and metastatic stage. Gemcitabine (GEM) is a gold standard chemotherapy used for PanCa treatment. However, GEM-acquired resistance in cancer cells is considered as a major setback for its continued clinical implementation. This phenomenon is evidently linked to de novo lipid synthesis. PanCa cells rely on de novo lipid synthesis, which is a prime event in survival and one of the key drivers for tumorigenesis, cancer progression, and drug resistance. Thus, the depletion of lipogenesis or lipid metabolism can not only improve treatment outcomes but also overcome chemoresistance, which is an unmet clinical need. Toward this effort, our study reports a unique paclitaxel−poly(lactic-co-glycolic acid) (PLGA) nanoparticles (PPNPs) formulation which can target lipid metabolism and improve anticancer efficacy of GEM in PanCa cells. PPNPs inhibit excessive lipid formation and alter membrane stability with compromised membrane integrity, which was confirmed by Fourier transform infrared and zeta potential measurements. The effective interference of PPNPs in lipid metabolic signaling was determined by reduction in the expression of FASN, ACC, lipin, and Cox-2 proteins. This molecular action profoundly enhances efficacy of GEM as evident through enhanced inhibitory effects on the tumorigenic and metastasis assays in PanCa cells. These data clearly suggest that the ablation of lipid metabolism might offer an innovative approach for the improved therapeutic outcome in PanCa patients.

Tumor Biology, 2019

Background : Pancreatic cancer (PanCa) is one of the most lethal malignancy with a very poor surv... more Background : Pancreatic cancer (PanCa) is one of the most lethal malignancy with a very poor survival rate in patients due to inadequate treatment options. Accumulating evidences suggest that tumor associated macrophages (TAMs) and reduce infiltration of CD8+ T-cell population provide tumor suppressive environment leading to advanced growth and metastasis of PanCa. Thus, targeting TAMs and enhancing infiltration of CD8+ T - cells to the tumor site by non-toxic agents could be an effective therapeutic approach for the management of PanCa. In this study, we demonstrate that a novel probiotic-derived agent (ferrichrome) inhibits pancreatic tumor growth in syngeneic mouse model via modulating TAMs and increasing infiltration of CD8+ T-cells. Methods : RAW264.7 cells, murine peritoneal macrophages, mouse pancreatic cancer cells (UN-KC-6141) were used for this study. Effect of ferrichrome on the expression of pro (IL-12, p40, iNOS, IL-6), anti-inflammatory cytokines (MRC1 and Arginase-1) and iron metabolism markers (ferritin and ferroportin) in macrophages and co-culture systems was analyzed by qPCR. Effect of ferrichrome on metastatic phenotypes of PanCa cells was analyzed in a co-culture model of RAW264.7 and UN-KC-6141 cells. Therapeutic efficacy of ferrichrome was determined in syngeneic mouse model. Tumor immune infiltrating cells were analyzed in excised tumors by FACS, double immunofluorescence and immunohistochemistry analyses. Results : Ferrichrome treatment reversed the polarization of M2 macrophages towards the M1 phenotype as observed by increase expression of IL-12p40, iNOS, IL-6 and decrease expression of MRC1 and Arginase-1. Ferrichrome significantly (P Conclusion : Our results strongly suggest that ferrichrome inhibits the tumor growth of PanCa via targeting TAMs and enhancing CD8+ T-cell infiltration. Ferrichrome could be used alone or in combination with current therapeutic regimens for the treatment of advanced PanCa. Citation Format: Mehdi Chaib, Bilal Bin Hafeez, Sonam Kumari, Mohammed Sikander, Hassan Mandil, Liza Makowski, Ajeeth Kumar Pingili, Elham Hatami, Advait Shetty, Dan Nirnoy, Murali Mohan Yallapu, Meena Jaggi, Subhash Chauhan. Ferrichrome suppresses pancreatic tumor growth via targeting TAMs and enhancing CD8+ T-cells infiltration [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 102.

Nanomedicine: Nanotechnology, Biology and Medicine, 2019

Pancreatic cancer (PanCa) is a major cause of cancer-related death due to limited therapeutic opt... more Pancreatic cancer (PanCa) is a major cause of cancer-related death due to limited therapeutic options. As pancreatic tumors are highly desmoplastic, they prevent appropriate uptake of therapeutic payloads. Thus, our objective is to develop a next-generation nanoparticle system for treating PanCa. We generated a multi-layered Pluronic F127 and polyvinyl alcohol stabilized and poly-L-lysine coated paclitaxel loaded poly(lactic-co-glycolic acid) nanoparticle formulation (PPNPs). This formulation exhibited optimal size (~160 nm) and negative Zeta potential (−6.02 mV), efficient lipid raft mediated internalization, pronounced inhibition in growth and metastasis in vitro, and in chemo-naive and chemo-exposed orthotopic xenograft mouse models. Additionally, PPNPs altered nanomechanical properties of PanCa cells as suggested by the increased elastic modulus in nanoindentation analyses. Immunohistochemistry of orthotopic tumors demonstrated decreased expression of tumorigenic and metastasis associated proteins (ki67, vimentin and slug) in PPNPs treated mice. These results suggest that PPNPs represent a viable and robust platform for (PanCa).

Frontiers in Cellular and Infection Microbiology, 2021

The exact global impact of leptospirosis is unknown due to inadequate surveillance systems in pla... more The exact global impact of leptospirosis is unknown due to inadequate surveillance systems in place in most low-income countries. In this study, we analyzed the differences in mouse inflammatory signatures involved in pathogenic versus non-pathogenic Leptospira recognition at 24h and 72h post infection. Injection of C3H-HeJ mice with non-pathogenic L. biflexa increased circulation of a few chemokines (5/21, 24%) without secretion of cytokines in blood that resulted in engagement of resident macrophages, dendritic cells, neutrophils and NK cells without engagement of T cells. In contrast, pathogenic L. interrogans induced circulation of a much higher panel of chemokines (18/21, 86%) and pro- and anti-inflammatory cytokines (11/19, 58%) in blood with a resulting signaling cascade leading to engagement of macrophages, dendritic cells, monocytes, NK cells and T cells without engagement of neutrophils. Although neutrophils do not appear to be engaged, a considerable number of chemokines ...

Asian Journal of Pharmaceutical and Clinical Research, 2017

The dry powder inhaler (DPI) has become widely known as a very attractive platform for drug deliv... more The dry powder inhaler (DPI) has become widely known as a very attractive platform for drug delivery. DPIs are being used for the treatment of asthma and chronic obstructive pulmonary disease by many patients. There are over 20 devices presently in the DPI market. DPIs are preferred over nebulizers and pressurized metered dose inhalers. However, some of the challenges of DPI are dependence on inspiratory flow (unsuitable for young children, elderly people), systemic absorption due to deposition of drug in deep lung (unsuitable for local diseases treatment), and increase in upper airway deposition of a large fraction of coarse particles. Hence, there is a need to address these unmet issues. The interpatient variation can be minimized by developing devices independent of patient’s inspiratory flow rate or active based powder mechanism. This article reviews DPI devices currently available, advantages of newly developed devices, and formulation technologies. The platform technologies ar...