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Full-Text Articles in Medicine and Health Sciences
Long-Acting Nanoformulated Antivirals For The Treatment And Prevention Of Hiv-1 And Hbv Infections, Dhruvkumar M. Soni Dr.
Long-Acting Nanoformulated Antivirals For The Treatment And Prevention Of Hiv-1 And Hbv Infections, Dhruvkumar M. Soni Dr.
Theses & Dissertations
While antiretroviral therapy (ART) has revolutionized treatment and prevention of human immunodeficiency virus type one (HIV-1) infection, regimen adherence, viral mutations, drug toxicities, stigma and pill fatigue are limitations. These have led to the development of long acting (LA) ART. These include, but are not limited to, implantable devices, new chemical entities, prodrug modifications and nanoformulations. To these ends, this thesis focues on the transformation of nucleoside reverse transcriptase inhibitors (NRTIs) into LA parenterals, While elusive, data from our laboratories demonstrated that modifications to the PROdrug and nucleoTide technology (ProTide) enables improvements in drug apparent half-life and tissue and cell …
Development Of A Long-Acting Nanoformulation Of Dolutegravir For Prevention And Treatment Of Hiv-1 Infection, Brady Sillman
Development Of A Long-Acting Nanoformulation Of Dolutegravir For Prevention And Treatment Of Hiv-1 Infection, Brady Sillman
Theses & Dissertations
Dolutegravir (DTG) is a potent human immunodeficiency virus type 1 (HIV-1) integrase strand-transfer inhibitor (INSTI) with a high barrier to viral drug resistance. However, opportunities to improve its profile abound. These include extending the drug’s apparent half-life, increasing penetrance to “putative” viral reservoirs, and reducing inherent toxicities. These highlight, in part, the need for long-acting, slow effective release antiretroviral therapy (LASER ART) delivery schemes. A long-acting (LA) DTG was made by synthesizing a hydrophobic and lipophilic prodrug encased with poloxamer (P407) surfactant. This modified DTG (MDTG) reduced systemic metabolism and polarity, increased lipophilicity and membrane permeability, improved encapsulation, and formed …