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  1. Article ; Online: Nanotherapeutic Approaches to Treat COVID-19-Induced Pulmonary Fibrosis.

    Kanvinde, Shrey / Deodhar, Suyash / Kulkarni, Tanmay A / Jogdeo, Chinmay M

    Biotech (Basel (Switzerland))

    2023  Volume 12, Issue 2

    Abstract: There have been significant collaborative efforts over the past three years to develop therapies against COVID-19. During this journey, there has also been a lot of focus on understanding at-risk groups of patients who either have pre-existing conditions ...

    Abstract There have been significant collaborative efforts over the past three years to develop therapies against COVID-19. During this journey, there has also been a lot of focus on understanding at-risk groups of patients who either have pre-existing conditions or have developed concomitant health conditions due to the impact of COVID-19 on the immune system. There was a high incidence of COVID-19-induced pulmonary fibrosis (PF) observed in patients. PF can cause significant morbidity and long-term disability and lead to death in the long run. Additionally, being a progressive disease, PF can also impact the patient for a long time after COVID infection and affect the overall quality of life. Although current therapies are being used as the mainstay for treating PF, there is no therapy specifically for COVID-induced PF. As observed in the treatment of other diseases, nanomedicine can show significant promise in overcoming the limitations of current anti-PF therapies. In this review, we summarize the efforts reported by various groups to develop nanomedicine therapeutics to treat COVID-induced PF. These therapies can potentially offer benefits in terms of targeted drug delivery to lungs, reduced toxicity, and ease of administration. Some of the nanotherapeutic approaches may provide benefits in terms of reduced immunogenicity owing to the tailored biological composition of the carrier as per the patient needs. In this review, we discuss cellular membrane-based nanodecoys, extracellular vesicles such as exosomes, and other nanoparticle-based approaches for potential treatment of COVID-induced PF.
    Language English
    Publishing date 2023-05-05
    Publishing country Switzerland
    Document type Journal Article ; Review
    ISSN 2673-6284
    ISSN (online) 2673-6284
    DOI 10.3390/biotech12020034
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: A Fully Integrated Online Platform For Real Time Monitoring Of Multiple Product Quality Attributes In Biopharmaceutical Processes For Monoclonal Antibody Therapeutics.

    Liu, Yang / Zhang, Chi / Chen, Jiangchao / Fernandez, Janice / Vellala, Pragna / Kulkarni, Tanmay A / Aguilar, Isaiah / Ritz, Diana / Lan, Kevin / Patel, Pramthesh / Liu, Aston

    Journal of pharmaceutical sciences

    2021  Volume 111, Issue 2, Page(s) 358–367

    Abstract: In response to FDA's call for Quality by Design (QbD) in biopharmaceutical product development, the biopharmaceutical industry has been developing highly sensitive and specific technologies in the monitoring and controlling of product quality attributes ... ...

    Abstract In response to FDA's call for Quality by Design (QbD) in biopharmaceutical product development, the biopharmaceutical industry has been developing highly sensitive and specific technologies in the monitoring and controlling of product quality attributes for bioprocesses. We previously published the successful application of an off-line multi-attribute method (MAM) to monitor more than 20 critical quality attributes (CQA) with superior sensitivity for the upstream process. To further remove the hurdles of laborious process sampling and sample preparation associated with the offline method, we present here a fully integrated MAM based online platform for automated real time online process monitoring. This integrated system includes Modular Automated Sampling Technology (MAST) based aseptic sampling, multi-function Sequential Injection Analysis (SIA) sample preparation, UHPLC separation and high-resolution mass spectrometry (HRMS) analysis. Continuous automated daily monitoring of a 17-day cell culture process was successfully demonstrated for a model monoclonal antibody (mAb) molecule with similar specificity and sensitivity as we reported earlier. To the best of our knowledge, this is the first report of an end-to-end automated online MAM system, which would allow the MAM to be applied to routine bioprocess monitoring, potentially replacing multiple conventional low resolution and low sensitivity off-line methods. The online HPLC or HPLC/MS platform could be easily adapted to support other processing steps such as downstream purification with minimal software re-configuration.
    MeSH term(s) Antibodies, Monoclonal/chemistry ; Biological Products/chemistry ; Cell Culture Techniques ; Chromatography, High Pressure Liquid ; Mass Spectrometry
    Chemical Substances Antibodies, Monoclonal ; Biological Products
    Language English
    Publishing date 2021-09-14
    Publishing country United States
    Document type Journal Article
    ZDB-ID 3151-3
    ISSN 1520-6017 ; 0022-3549
    ISSN (online) 1520-6017
    ISSN 0022-3549
    DOI 10.1016/j.xphs.2021.09.011
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Uf I Zs.50: Show issues Location:
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  3. Article ; Online: Dissecting VEGF-induced acute versus chronic vascular hyperpermeability: Essential roles of dimethylarginine dimethylaminohydrolase-1.

    Wang, Ying / Angom, Ramcharan Singh / Kulkarni, Tanmay A / Hoeppner, Luke H / Pal, Krishnendu / Wang, Enfeng / Tam, Alexander / Valiunas, Rachael A / Dutta, Shamit K / Ji, Baoan / Jarzebska, Natalia / Chen, Yingjie / Rodionov, Roman N / Mukhopadhyay, Debabrata

    iScience

    2021  Volume 24, Issue 10, Page(s) 103189

    Abstract: Vascular endothelial cell growth factor (VEGF) is a key regulator of vascular permeability. Herein we aim to understand how acute and chronic exposures of VEGF induce different levels of vascular permeability. We demonstrate that chronic VEGF exposure ... ...

    Abstract Vascular endothelial cell growth factor (VEGF) is a key regulator of vascular permeability. Herein we aim to understand how acute and chronic exposures of VEGF induce different levels of vascular permeability. We demonstrate that chronic VEGF exposure leads to decreased phosphorylation of VEGFR2 and c-Src as well as steady increases of nitric oxide (NO) as compared to that of acute exposure. Utilizing heat-inducible VEGF transgenic zebrafish (
    Language English
    Publishing date 2021-09-30
    Publishing country United States
    Document type Journal Article
    ISSN 2589-0042
    ISSN (online) 2589-0042
    DOI 10.1016/j.isci.2021.103189
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: The Immunopathobiology of SARS-CoV-2 Infection.

    Patel, Milankumar / Shahjin, Farah / Cohen, Jacob D / Hasan, Mahmudul / Machhi, Jatin / Chugh, Heerak / Singh, Snigdha / Das, Srijanee / Kulkarni, Tanmay A / Herskovitz, Jonathan / Meigs, Douglas D / Chandra, Ramesh / Hettie, Kenneth S / Mosley, R Lee / Kevadiya, Bhavesh D / Gendelman, Howard E

    FEMS microbiology reviews

    2021  Volume 45, Issue 6

    Abstract: Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can lead to coronavirus disease 2019 (COVID-19). Virus-specific immunity controls infection, transmission and disease severity. With respect to disease severity, a spectrum of ... ...

    Abstract Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can lead to coronavirus disease 2019 (COVID-19). Virus-specific immunity controls infection, transmission and disease severity. With respect to disease severity, a spectrum of clinical outcomes occur associated with age, genetics, comorbidities and immune responses in an infected person. Dysfunctions in innate and adaptive immunity commonly follow viral infection. These are heralded by altered innate mononuclear phagocyte differentiation, activation, intracellular killing and adaptive memory, effector, and regulatory T cell responses. All of such affect viral clearance and the progression of end-organ disease. Failures to produce effective controlled antiviral immunity leads to life-threatening end-organ disease that is typified by the acute respiratory distress syndrome. The most effective means to contain SARS-CoV-2 infection is by vaccination. While an arsenal of immunomodulators were developed for control of viral infection and subsequent COVID-19 disease, further research is required to enable therapeutic implementation.
    MeSH term(s) Adaptive Immunity ; COVID-19 ; Humans ; Immunity, Innate ; SARS-CoV-2
    Language English
    Publishing date 2021-06-23
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 283740-7
    ISSN 1574-6976 ; 0168-6445
    ISSN (online) 1574-6976
    ISSN 0168-6445
    DOI 10.1093/femsre/fuab035
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 2165: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

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  5. Article ; Online: Lipophilic nanocrystal prodrug-release defines the extended pharmacokinetic profiles of a year-long cabotegravir.

    Gautam, Nagsen / McMillan, JoEllyn M / Kumar, Devendra / Bade, Aditya N / Pan, Qiaoyu / Kulkarni, Tanmay A / Li, Wenkuan / Sillman, Brady / Smith, Nathan A / Shetty, Bhagya L Dyavar / Szlachetka, Adam / Edagwa, Benson J / Gendelman, Howard E / Alnouti, Yazen

    Nature communications

    2021  Volume 12, Issue 1, Page(s) 3453

    Abstract: A once every eight-week cabotegravir (CAB) long-acting parenteral is more effective than daily oral emtricitabine and tenofovir disoproxil fumarate in preventing human immunodeficiency virus type one (HIV-1) transmission. Extending CAB dosing to a yearly ...

    Abstract A once every eight-week cabotegravir (CAB) long-acting parenteral is more effective than daily oral emtricitabine and tenofovir disoproxil fumarate in preventing human immunodeficiency virus type one (HIV-1) transmission. Extending CAB dosing to a yearly injectable advances efforts for the elimination of viral transmission. Here we report rigor, reproducibility and mechanistic insights for a year-long CAB injectable. Pharmacokinetic (PK) profiles of this nanoformulated CAB prodrug (NM2CAB) are affirmed at three independent research laboratories. PK profiles in mice and rats show plasma CAB levels at or above the protein-adjusted 90% inhibitory concentration for a year after a single dose. Sustained native and prodrug concentrations are at the muscle injection site and in lymphoid tissues. The results parallel NM2CAB uptake and retention in human macrophages. NM2CAB nanocrystals are stable in blood and tissue homogenates. The long apparent drug half-life follows pH-dependent prodrug hydrolysis upon slow prodrug nanocrystal dissolution and absorption. In contrast, solubilized prodrug is hydrolyzed in hours in plasma and tissues from multiple mammalian species. No toxicities are observed in animals. These results affirm the pharmacological properties and extended apparent half-life for a nanoformulated CAB prodrug. The report serves to support the mechanistic design for drug formulation safety, rigor and reproducibility.
    MeSH term(s) Animals ; Drug Compounding ; Drug Liberation ; Endocytosis ; Humans ; Kinetics ; Lipids/chemistry ; Male ; Mice, Inbred BALB C ; Nanoparticles/chemistry ; Prodrugs/pharmacology ; Pyridones/administration & dosage ; Pyridones/blood ; Pyridones/pharmacokinetics ; Rats, Sprague-Dawley ; Reproducibility of Results ; Tissue Distribution ; Mice ; Rats
    Chemical Substances Lipids ; Prodrugs ; Pyridones ; cabotegravir (HMH0132Z1Q)
    Language English
    Publishing date 2021-06-08
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-021-23668-x
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: A year-long extended release nanoformulated cabotegravir prodrug.

    Kulkarni, Tanmay A / Bade, Aditya N / Sillman, Brady / Shetty, Bhagya Laxmi Dyavar / Wojtkiewicz, Melinda S / Gautam, Nagsen / Hilaire, James R / Sravanam, Sruthi / Szlachetka, Adam / Lamberty, Benjamin G / Morsey, Brenda M / Fox, Howard S / Alnouti, Yazen / McMillan, JoEllyn M / Mosley, R Lee / Meza, Jane / Domanico, Paul L / Yue, Tai-Yuen / Moore, Gary /
    Edagwa, Benson J / Gendelman, Howard E

    Nature materials

    2020  Volume 19, Issue 8, Page(s) 910–920

    Abstract: Long-acting cabotegravir (CAB) extends antiretroviral drug administration from daily to monthly. However, dosing volumes, injection site reactions and health-care oversight are obstacles towards a broad usage. The creation of poloxamer-coated hydrophobic ...

    Abstract Long-acting cabotegravir (CAB) extends antiretroviral drug administration from daily to monthly. However, dosing volumes, injection site reactions and health-care oversight are obstacles towards a broad usage. The creation of poloxamer-coated hydrophobic and lipophilic CAB prodrugs with controlled hydrolysis and tissue penetrance can overcome these obstacles. To such ends, fatty acid ester CAB nanocrystal prodrugs with 14, 18 and 22 added carbon chains were encased in biocompatible surfactants named NMCAB, NM2CAB and NM3CAB and tested for drug release, activation, cytotoxicity, antiretroviral activities, pharmacokinetics and biodistribution. Pharmacokinetics studies, performed in mice and rhesus macaques, with the lead 18-carbon ester chain NM2CAB, showed plasma CAB levels above the protein-adjusted 90% inhibitory concentration for up to a year. NM2CAB, compared with NMCAB and NM3CAB, demonstrated a prolonged drug release, plasma circulation time and tissue drug concentrations after a single 45 mg per kg body weight intramuscular injection. These prodrug modifications could substantially improve CAB's effectiveness.
    MeSH term(s) Animals ; Anti-Retroviral Agents/metabolism ; Anti-Retroviral Agents/pharmacology ; Anti-Retroviral Agents/toxicity ; Biological Transport ; Delayed-Action Preparations ; Drug Compounding ; Drug Interactions ; Drug Stability ; Mice ; Nanostructures/chemistry ; Prodrugs/chemistry ; Prodrugs/metabolism ; Pyridones/metabolism ; Pyridones/pharmacology ; Pyridones/toxicity
    Chemical Substances Anti-Retroviral Agents ; Delayed-Action Preparations ; Prodrugs ; Pyridones ; cabotegravir (HMH0132Z1Q)
    Language English
    Publishing date 2020-04-27
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2088679-2
    ISSN 1476-4660 ; 1476-1122
    ISSN (online) 1476-4660
    ISSN 1476-1122
    DOI 10.1038/s41563-020-0674-z
    Database MEDical Literature Analysis and Retrieval System OnLINE

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