IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v9y2018i1d10.1038_s41467-018-02885-x.html
   My bibliography  Save this article

Creation of a long-acting nanoformulated dolutegravir

Author

Listed:
  • Brady Sillman

    (University of Nebraska Medical Center)

  • Aditya N. Bade

    (University of Nebraska Medical Center)

  • Prasanta K. Dash

    (University of Nebraska Medical Center)

  • Biju Bhargavan

    (University of Nebraska Medical Center)

  • Ted Kocher

    (University of Nebraska Medical Center)

  • Saumi Mathews

    (University of Nebraska Medical Center)

  • Hang Su

    (University of Nebraska Medical Center)

  • Georgette D. Kanmogne

    (University of Nebraska Medical Center)

  • Larisa Y. Poluektova

    (University of Nebraska Medical Center)

  • Santhi Gorantla

    (University of Nebraska Medical Center)

  • JoEllyn McMillan

    (University of Nebraska Medical Center)

  • Nagsen Gautam

    (University of Nebraska Medical Center)

  • Yazen Alnouti

    (University of Nebraska Medical Center)

  • Benson Edagwa

    (University of Nebraska Medical Center)

  • Howard E. Gendelman

    (University of Nebraska Medical Center
    University of Nebraska Medical Center)

Abstract

Potent antiretroviral activities and a barrier to viral resistance characterize the human immunodeficiency virus type one (HIV-1) integrase strand transfer inhibitor dolutegravir (DTG). Herein, a long-acting parenteral DTG was created through chemical modification to improve treatment outcomes. A hydrophobic and lipophilic modified DTG prodrug is encapsulated into poloxamer nanoformulations (NMDTG) and characterized by size, shape, polydispersity, and stability. Retained intracytoplasmic NMDTG particles release drug from macrophages and attenuate viral replication and spread of virus to CD4+ T cells. Pharmacokinetic tests in Balb/cJ mice show blood DTG levels at, or above, its inhibitory concentration90 of 64 ng/mL for 56 days, and tissue DTG levels for 28 days. NMDTG protects humanized mice from parenteral challenge of the HIV-1ADA strain for two weeks. These results are a first step towards producing a long-acting DTG for human use by affecting drug apparent half-life, cell and tissue drug penetration, and antiretroviral potency.

Suggested Citation

  • Brady Sillman & Aditya N. Bade & Prasanta K. Dash & Biju Bhargavan & Ted Kocher & Saumi Mathews & Hang Su & Georgette D. Kanmogne & Larisa Y. Poluektova & Santhi Gorantla & JoEllyn McMillan & Nagsen G, 2018. "Creation of a long-acting nanoformulated dolutegravir," Nature Communications, Nature, vol. 9(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-02885-x
    DOI: 10.1038/s41467-018-02885-x
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-018-02885-x
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-018-02885-x?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Suyash Deodhar & Brady Sillman & Aditya N. Bade & Sean N. Avedissian & Anthony T. Podany & JoEllyn M. McMillan & Nagsen Gautam & Brandon Hanson & Bhagya L. Dyavar Shetty & Adam Szlachetka & Morgan Joh, 2022. "Transformation of dolutegravir into an ultra-long-acting parenteral prodrug formulation," Nature Communications, Nature, vol. 13(1), pages 1-15, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-02885-x. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.