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Development of an oral once-weekly drug delivery system for HIV antiretroviral therapy.
Kirtane, Ameya R; Abouzid, Omar; Minahan, Daniel; Bensel, Taylor; Hill, Alison L; Selinger, Christian; Bershteyn, Anna; Craig, Morgan; Mo, Shirley S; Mazdiyasni, Hormoz; Cleveland, Cody; Rogner, Jaimie; Lee, Young-Ah Lucy; Booth, Lucas; Javid, Farhad; Wu, Sarah J; Grant, Tyler; Bellinger, Andrew M; Nikolic, Boris; Hayward, Alison; Wood, Lowell; Eckhoff, Philip A; Nowak, Martin A; Langer, Robert; Traverso, Giovanni.
Affiliation
  • Kirtane AR; Department of Chemical Engineering and David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
  • Abouzid O; Department of Chemical Engineering and David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
  • Minahan D; Département Biosciences, Institut National des Sciences Appliquées de Lyon, 20 Avenue Albert Einstein, Villeurbanne, France, 69100.
  • Bensel T; Department of Chemical Engineering and David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
  • Hill AL; Department of Chemical Engineering and David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
  • Selinger C; Program for Evolutionary Dynamics, Harvard University, Cambridge, Massachusetts, 02138, USA.
  • Bershteyn A; Institute for Disease Modeling, Bellevue, WA, 98005, USA.
  • Craig M; Institute for Disease Modeling, Bellevue, WA, 98005, USA.
  • Mo SS; Program for Evolutionary Dynamics, Harvard University, Cambridge, Massachusetts, 02138, USA.
  • Mazdiyasni H; Program for Evolutionary Dynamics, Harvard University, Cambridge, Massachusetts, 02138, USA.
  • Cleveland C; Department of Chemical Engineering and David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
  • Rogner J; Department of Chemical Engineering and David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
  • Lee YL; Division of Gastroenterology Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA.
  • Booth L; Department of Chemical Engineering and David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
  • Javid F; Department of Chemical Engineering and David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
  • Wu SJ; Department of Chemical Engineering and David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
  • Bellinger AM; Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
  • Nikolic B; Lyndra Inc, Watertown, MA, 02472, USA.
  • Hayward A; Lyndra Inc, Watertown, MA, 02472, USA.
  • Wood L; Biomatics Capital, 1107 1st Avenue, Apartment 1305, Seattle, WA, 98101, USA.
  • Eckhoff PA; Department of Chemical Engineering and David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
  • Nowak MA; Institute for Disease Modeling, Bellevue, WA, 98005, USA.
  • Langer R; Institute for Disease Modeling, Bellevue, WA, 98005, USA.
  • Traverso G; Program for Evolutionary Dynamics, Harvard University, Cambridge, Massachusetts, 02138, USA.
Nat Commun ; 9(1): 2, 2018 01 09.
Article in En | MEDLINE | ID: mdl-29317618
ABSTRACT
The efficacy of antiretroviral therapy is significantly compromised by medication non-adherence. Long-acting enteral systems that can ease the burden of daily adherence have not yet been developed. Here we describe an oral dosage form composed of distinct drug-polymer matrices which achieved week-long systemic drug levels of the antiretrovirals dolutegravir, rilpivirine and cabotegravir in a pig. Simulations of viral dynamics and patient adherence patterns indicate that such systems would significantly reduce therapeutic failures and epidemiological modelling suggests that using such an intervention prophylactically could avert hundreds of thousands of new HIV cases. In sum, weekly administration of long-acting antiretrovirals via a novel oral dosage form is a promising intervention to help control the HIV epidemic worldwide.
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Full text: 1 Database: MEDLINE Main subject: Pyridones / Drug Delivery Systems / Anti-HIV Agents / Rilpivirine / Heterocyclic Compounds, 3-Ring Language: En Journal: Nat Commun Year: 2018 Type: Article Affiliation country: United States
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Full text: 1 Database: MEDLINE Main subject: Pyridones / Drug Delivery Systems / Anti-HIV Agents / Rilpivirine / Heterocyclic Compounds, 3-Ring Language: En Journal: Nat Commun Year: 2018 Type: Article Affiliation country: United States