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
Despite the world’s combined efforts, human immunodeficiency virus (HIV), the causative 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 increasin...
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MDPI AG
2020-12-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/1/340 |
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| author | Ilya Nifant’ev Andrei Siniavin Eduard Karamov Maxim Kosarev Sergey Kovalchuk Ali Turgiev Sergey Nametkin Vladimir Bagrov Alexander Tavtorkin Pavel Ivchenko |
| author_facet | Ilya Nifant’ev Andrei Siniavin Eduard Karamov Maxim Kosarev Sergey Kovalchuk Ali Turgiev Sergey Nametkin Vladimir Bagrov Alexander Tavtorkin Pavel Ivchenko |
| author_sort | Ilya Nifant’ev |
| collection | DOAJ |
| description | Despite the world’s combined efforts, human immunodeficiency virus (HIV), the causative 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 acceptance 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-<i>b</i>-PEPA) as candidates for developing a long-acting/controlled-release formulation of TFV. Two types of mPEG-<i>b</i>-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 adducts with TFD. Antiviral activity of [mPEG-<i>b</i>-PEPA]TFD or tenofovir disoproxil fumarate (TDF) was evaluated using the model of experimental HIV infection in vitro (MT-4/HIV-1<sub>IIIB</sub>). 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-<i>b</i>-PEPA adducts, thus demonstrating significant promise for further development of long-acting/controlled-release injectable TFV formulations. |
| first_indexed | 2024-03-10T13:38:37Z |
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| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T13:38:37Z |
| publishDate | 2020-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-491230d1ca4f4a5f9f2656ec9e95a1ca2023-11-21T03:13:16ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-12-0122134010.3390/ijms22010340A 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 CellsIlya Nifant’ev0Andrei Siniavin1Eduard Karamov2Maxim Kosarev3Sergey Kovalchuk4Ali Turgiev5Sergey Nametkin6Vladimir Bagrov7Alexander Tavtorkin8Pavel Ivchenko9Chemistry Department, M.V. Lomonosov Moscow State University, 1–3 Leninskie Gory, 119991 Moscow, RussiaN.F. Gamaleya National Research Center for Epidemiology and Microbiology MHRF, 18 Gamaleya Str., 123098 Moscow, RussiaN.F. Gamaleya National Research Center for Epidemiology and Microbiology MHRF, 18 Gamaleya Str., 123098 Moscow, RussiaChemistry Department, M.V. Lomonosov Moscow State University, 1–3 Leninskie Gory, 119991 Moscow, RussiaShemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 117997 Moscow, RussiaN.F. Gamaleya National Research Center for Epidemiology and Microbiology MHRF, 18 Gamaleya Str., 123098 Moscow, RussiaChemistry Department, M.V. Lomonosov Moscow State University, 1–3 Leninskie Gory, 119991 Moscow, RussiaChemistry Department, M.V. Lomonosov Moscow State University, 1–3 Leninskie Gory, 119991 Moscow, RussiaA.V. Topchiev Institute of Petrochemical Synthesis RAS, 29 Leninsky Pr., 119991 Moscow, RussiaChemistry Department, M.V. Lomonosov Moscow State University, 1–3 Leninskie Gory, 119991 Moscow, RussiaDespite the world’s combined efforts, human immunodeficiency virus (HIV), the causative 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 acceptance 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-<i>b</i>-PEPA) as candidates for developing a long-acting/controlled-release formulation of TFV. Two types of mPEG-<i>b</i>-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 adducts with TFD. Antiviral activity of [mPEG-<i>b</i>-PEPA]TFD or tenofovir disoproxil fumarate (TDF) was evaluated using the model of experimental HIV infection in vitro (MT-4/HIV-1<sub>IIIB</sub>). 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-<i>b</i>-PEPA adducts, thus demonstrating significant promise for further development of long-acting/controlled-release injectable TFV formulations.https://www.mdpi.com/1422-0067/22/1/340AIDScARTcontrolled releaseHIVinjectable formulationslong-acting drugs |
| spellingShingle | Ilya Nifant’ev Andrei Siniavin Eduard Karamov Maxim Kosarev Sergey Kovalchuk Ali Turgiev Sergey Nametkin Vladimir Bagrov Alexander Tavtorkin Pavel Ivchenko 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 International Journal of Molecular Sciences AIDS cART controlled release HIV injectable formulations long-acting drugs |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| topic | AIDS cART controlled release HIV injectable formulations long-acting drugs |
| url | https://www.mdpi.com/1422-0067/22/1/340 |
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