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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 …
Development Of Long-Acting Nanoformulated Abacavir Protides, Zhiyi Lin, Howard E. Gendelmant
Development Of Long-Acting Nanoformulated Abacavir Protides, Zhiyi Lin, Howard E. Gendelmant
Theses & Dissertations
Combination antiretroviral therapy (cART) for treatment of human immunodeficiency virus (HIV) infection demands life-long regimen adherence. Treatment interruptions lead to a lack of virologic control and the emergence of viral mutations and drug resistance. To address these, our laboratory developed long-acting (LA) parenteral administered nanoformulated abacavir prodrug (NMABC) by formulating myristoylated abacavir (MABC) with poloxamer 407 as stabilizer, which sustained ABC levels for up to 2 weeks with low levels of active drug metabolite (CBV-TP). To more significantly extend the apparent half-life of ABC and improve its antiretroviral activities, we developed second generation long-acting ABC prodrugs by ProTide technologies. This …