References

aids

ВИЧ-инфекция и иммуносупрессии

HIV Infection and Immunosuppressive Disorders

2077-9828

Baltic Medical Education Center

10.22328/2077-9828-2021-13-4-64-76

aids-680

Research Article

ОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯ

ORIGINAL STUDIES

Наносистемы для доставки антиретровирусных лекарственных средств: возможности, проблемы и перспективы

Nanosystems for the delivery of antiretroviral drugs: opportunities, problems, and prospects

https://orcid.org/0000-0003-0725-5455

Усеинова

А. Н.

Useinova*

А. N.

Усеинова Асие Наримановна — доцент кафедры базисной и клинической фармакологии

SPIN-код: 9031–2079

295051, Республика Крым, г. Симферополь, бул. Ленина, д. 5/7

Simferopol

mametova.as@mail.ru

https://orcid.org/0000-0003-4012-2523

Егорова

Е. А.

Mar’yanenko

S. P.

Егорова Елена Александровна — доцент кафедры базисной и клинической фармакологии

SPIN-код: 6856–7328

295051, Республика Крым, г. Симферополь, бул. Ленина, д. 5/7

Simferopol

egorovapharm@mail.ru

https://orcid.org/0000-0003-0765-5336

Марьяненко

С. П.

Egorova

E. A.

Марьяненко София Павловна — студентка III курса специальность «Лечебное дело»

295051, Республика Крым, г. Симферополь, бул. Ленина, д. 5/7

Simferopol

sofiya-maryanenko@mail.ru

https://orcid.org/0000-0003-3325-7948

Иванцова

Н. Л.

Ivancova

N. L.

Иванцова Наталья Леонидовна — доцент кафедры базисной и клинической фармакологии

SPIN-код: 3640–9298

295051, Республика Крым, г. Симферополь, бул. Ленина, д. 5/7

Simferopol

ivantsova69@mail.ru

Медицинская академия имени С. И. Георгиевского Крымского федерального университета имени В. И. ВернадскогоРоссияS. I. Georgievsky Medical Academy of V. I. Vernadsky Crimean Federal UniversityRussian Federation

2021

28012022

1346476

2022

Усеинова А.Н., Егорова Е.А., Марьяненко С.П., Иванцова Н.Л.

Useinova* А.N., Mar’yanenko S.P., Egorova E.A., Ivancova N.L.

Данная работа распространяется под лицензией Creative Commons Attribution 4.0.

This work is licensed under a Creative Commons Attribution 4.0 License.

https://hiv.bmoc-spb.ru/jour/article/view/680

Ведение пациентов с инфекцией, вызванной вирусом иммунодефицита человека (ВИЧ), сопровождается трудностями ранней диагностики, отсутствием специфической профилактики и дорогостоящим лечением. На данный момент от эпидемии, вызванной ВИЧ, от синдрома приобретенного иммунного дефицита (СПИД), умерло 32,7 млн человек по всему миру. Одним из наиболее важных направлений, позволяющих осуществлять контроль вирусной нагрузки и продлевать продолжительность жизни пациентов с ВИЧ, является наличие достаточного количества вариантов лечения ВИЧинфекции, доступных на каждой стадии заболевания, что увеличивает эффективность терапии и позволяет избежать и/или минимизировать побочные эффекты лекарств.Целью данной работы является обзор различных направлений в разработке новых лекарственных форм антиретровирусных средств на основе наносистем (НС) как препаратов, обладающих большей эффективностью для профилактики и лечения ВИЧ-инфекции.

Management of patients with an infection caused by the human immunodeficiency virus (HIV), is accompanied by difficulties of early diagnosis, expensive treatment, and the lack of specific prevention. To date, 32,7 million people worldwide have died due to the HIV epidemic from Acquired Immune Deficiency Syndrome (AIDS). One of the most important directions, to enable monitoring of viral load and extend the life expectancy of patients with HIV is to have a sufficient number of HIV treatment options available at each stage of the disease, which increases the effectiveness of treatment and allows to avoid and/or minimize the side effects of medication.The objective of this work is to review the various directions in the development of new dosage forms antiretroviral agents based nanosystems (NS) as the drugs hahavereater efficacy for the prevention and treatment of HIV infection.

ВИЧСПИДантиретровирусная терапиянаносистемынанотехнологии

HIVAIDSantiretroviral therapynanosystemsnanotechnology

References1

Parker R. The Global HIV/AIDS Pandemic, Structural Inequalities, and the Politics of International Health // American Journal of Public Health. 2002. Vol. 92, No. 3. Р. 343–347. DOI: 10.2105/ajph.92.3.343.

Nyamweya S., Hegedus A., Jaye A., Rowland-Jones S., Flanagan K., Macallan D. Comparing HIV-1, and HIV-2 infection: Lessons for viral immunopathogenesis // Reviews in Medical Virology. 2013. Vol. 23, No. 4. Р. 221–240. DOI: 10.1002/rmv.1739.

Shaw G., Hunter E. HIV Transmission // Cold Spring Harbor Perspectives in Medicine. 2012. Vol. 2, No. 11. Р. a006965-a006965. DOI: 10.1101/Csh Perspect.a006965.

Global HIV & AIDS statistics — 2020 fact sheet [Internet]. Unaids.org. 2021 [cited 20 April 2021]. Available from: http://www.unaids.org/en/resources/fact-sheet.

Dragojevic S., Ryu J., Raucher D. Polymer-Based Prodrugs: Improving Tumor Targeting and the Solubility of Small Molecule Drugs in Cancer Therapy // Molecules. 2015. Vol. 20, No. 12. Р. 21750–21769. DOI: 10.3390/molecules201219804.

Gilbert P., McKeague I., Eisen G., Mullins C., Guéye-NDiaye A., Mboup S. et al. Comparison of HIV-1 and HIV-2 infectivity from a prospective cohort study in Senegal // Statistics in Medicine. 2003. Vol. 22, No. 4. Р. 573–593. DOI: 10.1002/sim.1342.

Macheras P. Modeling in biopharmaceutics, pharmacokinetics,s, and pharmacodynamics. [Place of publication not identified]. // SPRINGER. Vol. 2018.

Kim P., Read S. Nanotechnology and HIV: potential applications for treatment and prevention // Wiley Interdisciplinary Reviews: Nanomedicine and Nanobiotechnology. 2010. Vol. 2, No. 6. Р. 693–702. DOI: 10.1002/wnan.118.

Nowacek A., Gendelman H. NanoART, neuroAID, S and CNS drug delivery // Nanomedicine. 2009. Vol. 4, No. 5. Р. 557–574. DOI: 10.2217/nnm.09.38.

Roy U., Rodríguez J., Barber P., das Neves J., Sarmento B., Nair M. The potential of HIV-1 nanotherapeutics: fromin vitrostudies to clinical trials // Nanomedicine. 2015. Vol. 10, No. 24. Р. 3597–3609. doi: 10.2217/nnm.15.160.

Aderibigbe B.A., Mukaya H.E. Nano-and microscale drug delivery systems // Polymer Therapeutics. 2017. Vol. 3. Р. 33–48. DOI: 10.1016/B978-0-323-52727-9.00003-0.

Foster V., Carraher C., Gebelein C. Applied bioactive polymeric materials // Plenum Press. 1989. Р. 103–114. New York. DOI: 10.1007/978- 1-4684-5610-3.

Van Damme L., Govinden R., Mirembe F., Guédou F., Solomon S., Becker M et al. Lack of Effectiveness of Cellulose Sulfate Gel for the Prevention of Vaginal HIV Transmission // New England Journal of Medicine. 2008. Vol. 359, No. 5. Р. 463–472. DOI: 10.1056/NEJMoa0707957.

Skoler-Karpoff S., Ramjee G., Ahmed K., Altini L., Plagianos M., Friedland B. et al. Efficacy of Carraguard for prevention of HIV infection in women in South Africa: a randomized, double-blind, placebo-controlled trial // The Lancet. 2008. Vol. 372, No. 9654. Р. 1977–1987. DOI: 10.1016/S0140-6736(08)61842-5.

Gunaseelan S., Debrah O., Wan L., Leibowitz M., Rabson A., Stein S. et al. Synthesis of Poly, No. ethylene glycol)-Based Saquinavir Prodrug Conjugates and Assessment of Release and Anti-HIV-1 Bioactivity Using a Novel Protease Inhibition Assay // Bioconjugate Chemistry. 2004. Vol. 15, No. 6. Р. 1322–1333. DOI: 10.1021/bc0498875.

Chen Y., Hung Y., Liau I., Huang G. Assessment of the In Vivo Toxicity of Gold Nanoparticles // Nanoscale Research Letters. 2009. Vol. 4, No. 8. Р. 858–864. DOI: 10.1007/s11671-009-9334-6.

Zhou Y., Peng Z., Seven E., Leblanc R. Crossing the blood-brain barrier with nanoparticles // Journal of Controlled Release. 2018. Vol. 270. Р. 290–303. DOI: 10.1016/j.jconrel.2017.12.015.

Martins C., Araújo F., Gomes M., Fernandes C., Nunes R., Li W. et al. Using microfluidic platforms to develop CNS-targeted polymeric nanoparticles for HIV therapy // European Journal of Pharmaceutics and Biopharmaceutics. 2019. Vol. 138. Р. 111–124. DOI: 10.1016/j.ejpb.2018.01.014.

Vlieghe P., Clerc T., Pannecouque C., Witvrouw M., De Clercq E., Salles J et al. Synthesis of New Covalently Bound–Carrageenan−ZDV Conjugates with Improved Anti-HIV Activities // Journal of Medicinal Chemistry. 2002. Vol. 45, No. 6. Р. 1275–1283. DOI: 10.1021/jm010969d.

Surve D., Jindal A. Recent advances in long-acting nanoformulations for delivery of antiretroviral drugs // Journal of Controlled Release. 2020. Vol. 324. Р. 379–404. DOI: 10.1016/j.jconrel.2020.05.022.

Kumar L., Verma S., Prasad D., Bhardwaj A., Vaidya B, Jain A. Nanotechnology: A magic bullet for HIV AIDS treatment // Artificial Cells, Nanomedicine, and Biotechnology. 2014. Vol. 43, No. 2. Р. 71–86. DOI: 10.3109/21691401.2014.883400.

Moghimi S., Szebeni J. Stealth liposomes and long-circulating nanoparticles: critical issues in pharmacokinetics, opsonization and protein-binding properties // Progress in Lipid Research. 2003. Vol. 42, No. 6. Р. 463–478. DOI: 10.1016/s0163-7827, No. 03)00033-x.

Geszke-Moritz M., Moritz M. Solid lipid nanoparticles as attractive drug vehicles: Composition, properties and therapeutic strategies // Materials Science and Engineering. 2016. Vol. 68. Р. 982–994. DOI: 10.1016/j.msec.2016.05.119.

Garg M., Jain N. Reduced hematopoietic toxicity, enhanced cellular uptake and altered pharmacokinetics of azidothymidine loaded galactosylated liposomes // Journal of Drug Targeting. 2006. Vol. 14, No. 1. Р. 1–11. DOI: 10.1080/10611860500525370.

Dubey V., Mishra D., Nahar M., Jain V., Jain N. Enhanced transdermal delivery of an anti-HIV agent via ethanolic liposomes // Nanomedicine: Nanotechnology, Biology, and Medicine. 2010. Vol. 6, No. 4. Р. 590–596. DOI: 10.1016/j.nano.2010.01.002.

Shao J., Kraft J., Li B., Yu J., Freeling J., Koehn J et al.Nano drug formulations to enhance HIV drug exposure in lymphoid tissues and cells: clinical significance and potential impact on treatment and eradication of HIV/AIDS // Nanomedicine. 2016. Vol. 11, No. 5. Р. 545–564. DOI: 10.2217/nnm.16.1.

Ho R., Yu J., Li B., Kraft J., Freeling J., Koehn J et al. Systems Approach to targeted and long-acting HIV/AIDS therapy // Drug Delivery and Translational Research. 2015. Vol. 5, No. 6. Р. 531–539. DOI: 10.1007/s13346-015-0254-y.

Moyo S., Wilkinson E., Novitsky V., Vandormael A., Gaseitsiwe S., Essex M et al. Identifying Recent HIV Infections: From Serological Assays to Genomics // Viruses. 2015. Vol. 7, No. 10. Р. 5508–5524. DOI: 10.3390/v7102887.

Kuo Y., Su F. Transport of stavudine, delavirdine, and saquinavir across the blood-brain barrier by poly butyl cyanoacrylate, methylmethacrylatesulfopropylmethacrylate, and solid lipid nanoparticles // International Journal of Pharmaceutics. 2007. Vol. 340, No. 1–2. Р. 143–152. DOI: 10.1016/j.ijpharm.2007.03.012.

Almeida A., Souto E. Solid lipid nanoparticles as a drug delivery system for peptides and proteins // Advanced Drug Delivery Reviews. 2007. Vol. 59, No. 6. Р. 478–490. DOI: 10.1016/j.addr.2007.04.007.

Kammari R., Das N., Das S. Nanoparticulate Systems for Therapeutic and Diagnostic Applications // Emerging Nanotechnologies for Diagnostics, Drug Delivery and Medical Devices. 2017. Vol. 105–144. DOI: 10.1016/B978-0-323-42978-8.00006-1.

Becker Peres L, Becker Peres L, de Araújo P, Sayer C. Solid lipid nanoparticles for encapsulation of hydrophilic drugs by an organic solvent-free double emulsion technique // Colloids and Surfaces B: Biointerfaces. 2016. Vol. 140. Р. 317–323. DOI: 10.1016/j.colsurfb.2015.12.033.

Doktorovová S, Santos D, Costa I, Andreani T, Souto E, Silva A. Cationic solid lipid nanoparticles interfere with the activity of antioxidant enzymes in hepatocellular carcinoma cells // International Journal of Pharmaceutics. 2014. Vol. 471, No. 1–2. Р. 18–27. DOI: 10.1016/j.ijpharm.2014.05.011.

Aji Alex M, Chacko A, Jose S, Souto E. Lopinavir loaded solid lipid nanoparticles, No. SLN) for intestinal lymphatic targeting // European Journal of Pharmaceutical Sciences. 2011. Vol. 42, No. 1–2. Р. 11–18. DOI: 10.1016/j.ejps.2010.10.002.

Makwana V., Jain R., Patel K., Nivsarkar M., Joshi A. Solid lipid nanoparticles, No. SLN) of Efavirenz as lymph targeting drug delivery system: Elucidation of the mechanism of uptake using chylomicron flow blocking approach // International Journal of Pharmaceutics. 2015. Vol. 495, No. 1. Р. 439–446. DOI: 10.1016/j.ijpharm.2015.09.014.

Fahr A., Liu X. Drug delivery strategies for poorly water-soluble drugs // Expert Opinion on Drug Delivery. 2007. Vol. 4. Р. 403–416. DOI: 10.1517/17425247.4.4.403.

Gaur P., Mishra S., Bajpai M., Mishra A. Enhanced Oral Bioavailability of Efavirenz by Solid Lipid Nanoparticles: In VitroDrug Release and Pharmacokinetics Studies // BioMed Research International. 2014. Р. 1–9. DOI: 10.1155/2014/363404.

Chiappetta D., Hocht C., Taira C., Sosnik A. Efavirenz-loaded polymeric micelles for pediatric anti-HIV pharmacotherapy with significantly higher oral bioavailability // Nanomedicine. 2010. Vol. 5, No. 1. Р. 11–23. DOI: 10.2217/nnm.09.90.

Tan C., Wang Y., Fan W. Exploring Polymeric Micelles for Improved Delivery of Anticancer Agents: Recent Developments in Preclinical Studies // Pharmaceutics. 2013. Vol. 5, No. 4. Р. 201–219. DOI: 10.3390/pharmaceutics5010201.

Chiappetta D., Hocht C., Taira C., Sosnik A. Oral pharmacokinetics of the anti-HIV efavirenz encapsulated within polymeric micelles // Biomaterials. 2011. Vol. 32, No. 9. Р. 2379–2387. DOI: 10.1016/j.biomaterials.2010.11.082.

Chiappetta D., Hocht C., Opezzo J., Sosnik A. Intranasal administration of antiretroviral-loaded micelles for anatomical targeting to the brain in HIV // Nanomedicine. 2013. Vol. 8, No. 2. Р. 223–237. doi: 10.2217/nnm.12.104.

Seremeta K., Chiappetta D., Sosnik A. Poly (e-caprolactone), Eudragit® RS 100 and poly, No. e-caprolactone)/Eudragit® RS 100 blend submicron particles for the sustained release of the antiretroviral efavirenz // Colloids and Surfaces B: Biointerfaces. 2013. Vol. 102. Р. 441–449. DOI: 10.1016/j.colsurfb.2012.06.038.

Mohideen M., Quijano E., Song E., Deng Y., Panse G., Zhang W. et al. Degradable bioadhesive nanoparticles for prolonged intravaginal delivery and retention of elvitegravir // Biomaterials. 2017. Vol. 144. Р. 144–154. DOI: 10.1016/j.biomaterials.2017.08.029.

Farias E.D., Bouchet L.M., Brunetti V., Strumia M.C. Dendrimers and dendronized materials as nanocarriers // Grumezescu A., Ficai D., editors. Nanostructures for Novel Therapy: Synthesis, Characterization, and Applications // Elsevier. 2017. Vol. 429–456. DOI: 10.1016/j.arabjc.2012.09.010.

Barrios-Gumiel A., Sepúlveda-Crespo D., Jiménez J., Gómez R., Muñoz-Fernández M., de la Mata F. Dendronized magnetic nanoparticles for HIV-1 capture and rapid diagnostic // Colloids and Surfaces B: Biointerfaces. 2019. Vol. 181. Р. 360–368. doi: 10.1016/j.colsurfb.2019.05.050.

Dey P, Bergmann T., Cuellar-Camacho J., Ehrmann S., Chowdhury M., Zhang M., Dahmani I., Haag R., Azab W. Multivalent Flexible Nanogels Exhibit Broad-Spectrum Antiviral Activity by Blocking Virus Entry // ACS Nano. 2018. Vol. 12, No. 7. Р. 6429–6442. DOI: 10.1021/acsnano.8b01616.

Rupp R., Rosenthal S.L., Stanberry LR. Viva Gel (SPL7013 Gel.) a candidate dendrimer-microbicide for the prevention of HIV and HSV infection // Int J Nanomedicine. 2007. Vol. 2, No. 4. Р. 561–566. DOI: 10.2147/DDDT.S133170.

Macchione M., Biglione C., Strumia M. Design, Synthesis and Architectures of Hybrid Nanomaterials for Therapy and Diagnosis Applications // Polymers. 2018. Vol. 10, No. 5. Р. 527. DOI: 10.3390/polym10050527.

McCarthy T., Karellas P., Henderson S., Giannis M., O’Keefe D., Heery G. et al. Dendrimers as Drugs: Discovery and Preclinical and Clinical Development of Dendrimer-Based Microbicides for HIV and STI Prevention // Molecular Pharmaceutics. 2005. Vol. 2, No. 4. Р. 312–318. DOI: 10.1021/mp050023q.

SPL7013 Gel — Male Tolerance Study — Full-Text View — ClinicalTrials.gov [Internet]. Clinicaltrials.gov. 2021 [cited 20 April 2021]. Available from: https://clinicaltrials.gov/ct2/show/NCT00370357.

Retention and Duration of Activity of SPL7013 (VivaGel®) After Vaginal Dosing. Full Text View — ClinicalTrials.gov [Internet]. Clinicaltrials.gov. 2021 [cited 20 April 2021]. Available from: https://clinicaltrials.gov/ct2/show/NCT00740584.

Dutta T., Jain N. Targeting potential and anti-HIV activity of lamivudine loaded mannosylated poly (propylene imine) dendrimer // Biochimica et Biophysica Acta (BBA) — General Subjects. 2007. Vol. 1770, No. 4. Р. 681–686. DOI: 10.1016/j.bbagen.2006.12.007.

Gajbhiye V., Ganesh N., Barve J., Jain N. Synthesis, characterization and targeting potential of zidovudine loaded sialic acid conjugated-mannosylated poly (propylene imine) dendrimers // European Journal of Pharmaceutical Sciences. 2013. Vol. 48, No. 4–5. Р. 668–679. DOI: 10.1016/j.ejps.2012.12.027.

Kannan S., Dai H., Navath R., Balakrishnan B., Jyoti A., Janisse J et al. Dendrimer-Based Postnatal Therapy for Neuroinflammation and Cerebral Palsy in a Rabbit Model // Science Translational Medicine. 2012. Vol. 4, No. 130. Р. 130ra46–130ra46. DOI: 10.1126/scitranslmed.3003162.

Nance E., Kambhampati S., Smith E., Zhang Z., Zhang F., Singh S. et al. Dendrimer-mediated delivery of N-acetyl cysteine to microglia in a mouse model of Rett syndrome // Journal of Neuroinflammation. 2017. Vol. 14, No. 1. doi: 10.1186/s12974-017-1004-5.

Hong S., Bielinska A., Mecke A., Keszler B., Beals J., Shi X. et al. Interaction of Poly, No. amidoamine) Dendrimers with Supported Lipid Bilayers and Cells: Hole Formation and the Relation to Transport // Bioconjugate Chemistry. 2004. Vol. 15, No. 4. Р. 774–782. DOI: 10.1021/bc049962b.

Kukowska-Latallo J., Patri A.K., Chen C., Ge S., Cao Z., Kotlyar A., East A.T., Baker J.R. Targeted gadolinium-loaded dendrimer nanoparticles for tumor-specific magnetic resonance contrast enhancement // International Journal of Nanomedicine. 2008. Vol. 201. DOI: 10.2147/IJN.S2696.

Baert L., van ‘t Klooster G., Dries W., François M., Wouters A., Basstanie E et al. Development of a long-acting injectable formulation with nanoparticles of rilpivirine (TMC278) for HIV treatment // European Journal of Pharmaceutics and Biopharmaceutics. 2009. Vol. 72, No. 3. Р. 502–508. DOI: 10.1016/j.ejpb.2009.03.006.

Macchione M., Sacarelli M., Racca A., Biglione C., Panzetta-Dutari G., Strumia M. Dual-responsive nanogels based on oligo (ethylene glycol) methacrylates and acidic co-monomers // Soft Matter. 2019. Vol. 15, No. 47. Р. 9700–9709. DOI: 10.1039/c9sm01180c.

Das S, Bharadwaj P., Bilal M., Barani M., Rahdar A., Taboada P., Bunga S., Kyzas G. Stimuli-Responsive Polymeric Nanocarriers for Drug Delivery, Imaging, and Theragnosis // Polymers. 2020. Vol. 12, No. 6. Р. 1397. DOI: 10.3390/polym12061397.

Molina M., Asadian-Birjand M., Balach J., Bergueiro J., Miceli E., Calderón M. Stimuli-responsive nanogel composites and their application in nanomedicine // Chemical Society Reviews. 2015. Vol. 44, No. 17. Р. 6161–6186. DOI: 10.1039/c5cs00199d.

Wang H., Chen Q., Zhou S. Carbon-based hybrid nanogels: a synergistic nanoplatforms for combined biosensing, bioimaging, and responsive drug delivery // Chemical Society Reviews. 2018. Vol. 47, No. 11. Р. 4198–4232. DOI: 10.1039/c7cs00399d.

Ho E., Chen., Dash., Sayre C., Davies N., Gu et al. Novel intravaginal nanomedicine for the targeted delivery of saquinavir to CD4+ immune cells // International Journal of Nanomedicine. 2013. Vol. 8. Р. 2847–2853. DOI: 10.2147/IJN.S46958.

Forbes C., Lowry D., Geer L., Veazey R., Shattock R, Klasse P. et al. Non-aqueous silicone elastomer gels as a vaginal microbicide delivery system for the HIV-1 entry inhibitor maraviroc // Journal of Controlled Release. 2011. Vol. 156, No. 2. Р. 161–169. DOI: 10.1016/j.jconrel.2011.08.006.

Jiang Y., Emau P., Cairns J., Flanary L., Morton W., McCarthy T. et al. SPL7013 Gel as a Topical Microbicide for Prevention of Vaginal Transmission of SHIV89.6P in Macaques // AIDS Research and Human Retroviruses. 2005. Vol. 21, No. 3. Р. 207–213. DOI: 10.1089/aid.2005.21.207.

Spreen W., Margolis D., Pottage J. Long-acting injectable antiretrovirals for HIV treatment and prevention // Current Opinion in HIV and AIDS. 2013. Vol. 8, No. 6. Р. 565–571. DOI: 10.1097/COH.0000000000000002.

Malamatari M., Taylor K., Malamataris S., Douroumis D., Kachrimanis K. Pharmaceutical nanocrystals: production by wet milling and applications // Drug Discovery Today. 2018. Vol. 23, No. 3. Р. 534–547. DOI: 10.1016/j.drudis.2018.01.016.

Van ‘t Klooster G., Hoeben E., Borghys H., Looszova A., Bouche M., van Velsen F et al. Pharmacokinetics and Disposition of Rilpivirine (TMC278) Nanosuspension as a Long-Acting Injectable Antiretroviral Formulation // Antimicrobial Agents and Chemotherapy. 2010. Vol. 54, No. 5. Р. 2042–2050. DOI: 10.1128/AAC.01529-09.

Jackson A., Else L., Mesquita P., Egan D., Back D., Karolia Z., et al. A Compartmental Pharmacokinetic Evaluation of Long-Acting Rilpivirine in HIV-Negative Volunteers for Pre-Exposure Prophylaxis // Clinical Pharmacology & Therapeutics. 2014. Vol. 96, No. 3. Р. 314–323. DOI: 10.1038/clpt.2014.118.

Efficacy, Safety, and Tolerability Study of Long-acting Cabotegravir Plus Long-acting Rilpivirine (No. CAB LA + RPV LA) in Human-immunodeficiency Virus-1, No. HIV-1. Infected Adults — Full-Text View — ClinicalTrials.gov [Internet]. Clinicaltrials.gov. 2021 [cited 20 April 2021]. Available from: https://clinicaltrials.gov/ct2/show/NCT03299049.

Monroe M., Flexner C., Cui H. Harnessing nanostructured systems for improved treatment and prevention of HIV disease // Bioengineering & translational medicine. 2021. Vol. 3, No. 2. Р. 102–123. DOI: 10.1002/btm2.10096.

Study to Evaluate the Efficacy, Safety, and Tolerability of Long-acting Intramuscular Cabotegravir and Rilpivirine for Maintenance of Virologic Suppression Following Switch From an Integrase Inhibitor in HIV-1 Infected Therapy Naive Participants — Full-Text View — ClinicalTrials.gov [Internet]. Clinicaltrials.gov. 2021 [cited 20 April 2021]. Available from: https://clinicaltrials.gov/ct2/show/NCT02938520.

Margolis D., Gonzalez-Garcia J., Stellbrink H., Eron J., Yazdanpanah Y., Podzamczer D et al. Long-acting intramuscular cabotegravir and rilpivirine in adults with HIV-1 infection (LATTE-2) 96-week results of a randomized, open-label, phase 2b, non-inferiority trial // The Lancet. 2017. Vol. 390, No. 10101. Р. 1499–1510. DOI: 10.1016/S0140-6736, No. 17)31917-7.

Araínga M., Edagwa B., Mosley R., Poluektova L., Gorantla S., Gendelman H. A mature macrophage is a principal HIV-1 cellular reservoir in humanized mice after treatment with long-acting antiretroviral therapy // Retrovirology. 2017. Vol. 14, No. 1. doi: 10.1186/s12977-017-0344-7.

Zhou T., Su H., Dash P., Lin Z., Dyavar Shetty B., Kocher T. et al. Creation of a nano formulated cabotegravir prodrug with improved antiretroviral profiles // Biomaterials. 2018. Vol. 151. Р. 53–65. DOI: 10.1016/j.biomaterials.2017.10.023.

Dou H., Destache C., Morehead J., Mosley R., Boska M., Kingsley J. et al. Development of a macrophage-based nanoparticle platform for antiretroviral drug delivery // Blood. 2006. Vol. 108, No. 8. Р. 2827–2835. DOI: 10.1182/blood-2006-03-012534.

Buchanan A., Cunningham C. Advances and Failures in Preventing Perinatal Human Immunodeficiency Virus Infection // Clinical Microbiology Reviews. 2009. Vol. 22, No. 3. Р. 493–507. DOI: 10.1128/CMR.00054-08.

The authors declare that there are no conflicts of interest present.