A new approach to developing long-acting injectable formulations of anti-HIV drugs: Poly(ethylene phosphoric acid) block copolymers increase the efficiency of tenofovir against HIV-1 in MT-4 cells

Ilya Nifant’ev, Andrei Siniavin, Eduard Karamov, Maxim Kosarev, Sergey Kovalchuk, Ali Turgiev, Sergey Nametkin, Vladimir Bagrov, Alexander Tavtorkin, Pavel Ivchenko

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Despite the world’s combined efforts, human immunodeficiency virus (HIV), the causa-tive agent of AIDS, remains one of the world’s most serious public health challenges. High genetic variability of HIV complicates the development of anti-HIV vaccine, and there is an actual clinical need for increasing the efficiency of anti-HIV drugs in terms of targeted delivery and controlled release. Tenofovir (TFV), a nucleotide-analog reverse transcriptase inhibitor, has gained wide ac-ceptance as a drug for pre-exposure prophylaxis or treatment of HIV infection. In our study, we explored the potential of tenofovir disoproxil (TFD) adducts with block copolymers of poly(ethylene glycol) monomethyl ether and poly(ethylene phosphoric acid) (mPEG-b-PEPA) as candidates for developing a long-acting/controlled-release formulation of TFV. Two types of mPEG-b-PEPA with numbers of ethylene phosphoric acid (EPA) fragments of 13 and 49 were synthesized by catalytic ring-opening polymerization, and used for preparing four types of ad-ducts with TFD. Antiviral activity of [mPEG-b-PEPA]TFD or tenofovir disoproxil fumarate (TDF) was evaluated using the model of experimental HIV infection in vitro (MT-4/HIV-1IIIB). Judging by the values of the selectivity index (SI), TFD exhibited an up to 14-fold higher anti-HIV activity in the form of mPEG-b-PEPA adducts, thus demonstrating significant promise for further development of long-acting/controlled-release injectable TFV formulations.

Original languageEnglish (US)
Article number340
Pages (from-to)1-16
Number of pages16
JournalInternational journal of molecular sciences
Volume22
Issue number1
DOIs
StatePublished - Jan 1 2021
Externally publishedYes

Keywords

  • AIDS
  • CART
  • Controlled release
  • HIV
  • Injectable formulations
  • Long-acting drugs
  • Poly(phosphoric acid)
  • Polyphosphoesters
  • PrEP
  • Ring-opening polymerization
  • Tenofovir

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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