Skip to main content
SpringerLink
Log in
Book cover

Nanobiotechnology in Neurodegenerative Diseases pp 241–266Cite as

Nanomedicines for Improved Antiretroviral Therapy in Neuro-AIDS

  • Chapter
  • First Online:

  • 569 Accesses

Abstract

Human immunodeficiency virus is neurotropic which invades the central nervous system (CNS) in early course of systemic infection and makes the CNS an important dominant reservoir with the capacity to supply virus in low/undetectable viremia. Neuro-AIDS is the major upcoming issue among long-term seropositive survivors as a consequence of incompetence of antiretroviral in complete eradication of HIV from the CNS. Justification behind the low CNS concentration of antiretroviral is anatomical barrier and physicochemical properties of antiretrovirals. Some unmet needs in neuro-AIDS treatment are simplified CNS-targeted treatment regimen and disease-modifying therapies. Target-specific, safe, and controllable nanomedicines have been extensively studied, with particular success, to overcome the natural barriers to the antiretroviral drug delivery posed by the CNS anatomy, histology, and physiology. This chapter insight on current understanding of neuro-AIDS and the pathological mechanisms involved several limitations to the eradication of latent reservoirs and approaches to circumvent these limitations by state-of-the-art nanomedicines.

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Abbreviations

ABC:

ATP-binding cassette

ADC:

AIDS dementia complex

AIDS:

Acquired immunodeficiency syndrome

ARV:

Antiretroviral

BBB:

Blood-brain barrier

BCRP:

Breast cancer resistance protein

BCSFB:

Blood-cerebrospinal fluid barrier

BMECs:

Brain microvessel endothelial cells

BMVECs:

Brain microvascular endothelial cells

cART:

Combination antiretroviral therapy

CCR5:

C-C chemokine receptor type 5

CD4:

Cluster of differentiation 4

CNS:

Central nervous system

CSF:

Cerebrospinal fluid

CSFB:

Cerebrospinal fluid-brain barrier

CXCR4:

C-X-C chemokine receptor type 4

gp120:

Glycoprotein 120

HAART:

Highly active antiretroviral therapy

HAND:

HIV-associated neurocognitive disorders

hCMEC/D3:

Human cerebral microvascular endothelial cell line

HIV:

Human immunodeficiency virus

NLCs:

Nanostructured lipid carriers

PLA:

Polylactic acid

PLGA:

Poly(D,L-lactic-co-glycolic acid)

siRNA:

Small interfering ribonucleic acid

SIV:

Simian immunodeficiency virus

SLN:

Solid lipid nanoparticle

Vpr:

Viral protein R

References

  • Albright A, Soldan S, Gonzalez-Scarano F (2003) Pathogenesis of human immunodeficiency virus-induced neurological disease. J Neurovirol 9:222–227

    Article  CAS  PubMed  Google Scholar 

  • Alghananeem AM, Saeed H, Florence R, Yokel R, Malkawi A (2010) Intranasal drug didanosine-loadedchitosan nanoparticles for brain targeting; an attractive route against ing=fections caused by AIDS viruses. J Drug Targeting 18:381–388

    Google Scholar 

  • Ballabh P, Braun A, Nedergaard M (2004) The blood–brain barrier: an overview: structure, regulation, and clinical implications. Neurobiol Dis 16:1–13

    Article  CAS  PubMed  Google Scholar 

  • Barbi M, Carvalho C, Kiill C, Barud H, Santagneli S, Ribeiro S, Gremião M (2015) Preparation and characterization of chitosan nanoparticles for zidovudine nasal delivery. J Nanosci Nanotechnol 15:865–874

    Article  CAS  Google Scholar 

  • Batrakova E, Li S, Miller D, Kabanov A (1999) Pluronic P85 increases permeability of a broad spectrum of drugs in polarized BBMEC and Caco-2 cell monolayers. Pharm Res 16:1366–1372

    Article  CAS  PubMed  Google Scholar 

  • Belgamwar A, Khan S, Yeole P (2018) Intranasal chitosan-g-HPβCD nanoparticles of efavirenz for the CNS targeting. Artif Cell Nanomed Biotechnol 46:374–386

    Article  CAS  Google Scholar 

  • Belgamwar A, Khan S, Yeole P (2019) Intranasal dolutegravir sodium loaded nanoparticles of hydroxypropyl-betacyclodextrin for brain delivery in neuro-AIDS. J Drug Deliv Sci Technol 52:1008–1020

    Article  CAS  Google Scholar 

  • Bell J (2004) An update on the neuropathology of HIV in the HAART era. Histopathology 45:549–559

    Article  CAS  PubMed  Google Scholar 

  • Blasi P, Giovagnoli S, Schoubben A, Ricci M, Rossi C (2007) Solid lipid nanoparticles for targeted brain drug delivery. Adv Drug Deliv Rev 59:454–477

    Article  CAS  PubMed  Google Scholar 

  • Chattopadhyay N, Zastre J, Wong HL, Wu XY, Bendayan R (2008) Solid lipid nanoparticles enhance the delivery of the HIV protease inhibitor, atazanavir, by a human brain endothelial cell line. Pharm Res 25:2262–2271

    Article  CAS  PubMed  Google Scholar 

  • Chiappetta D, Hocht C, Opezzo J, Sosnik A (2013) Intranasal administration of antiretroviral-loaded micelles for anatomical targeting to the brain in HIV. Nanomedicine 8:223–237

    Article  CAS  PubMed  Google Scholar 

  • Connor R, Sheridan K, Ceradini D, Choe S, Landau N (1997) Change in coreceotor use correlates with disease progression in HIV-1 infected individuals. J Exp Med 185:621–628

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dalpiaz A, Fogagnolo M, Ferraro L, Capuzzo A, Pavan B, Rassu G, Salis A, Giunchedi P, Gavini E (2015) Nasal chitosan microparticles target a zidovudine prodrug to brain HIV sanctuaries. Antiviral Res 123:146–157

    Article  CAS  PubMed  Google Scholar 

  • Das M, Chakraborty T (2015) Progress in brain delivery of anti-HIV drugs. J Appl Pharm Sci 5:154–164

    Article  CAS  Google Scholar 

  • Das S, Ng W, Tan R (2012) Are nanostructured lipid carriers (NLCs) better than solid lipid nanoparticles (SLNs): development, characterizations and comparative evaluations of clotrimazole-loaded SLNs and NLCs? Eur J Pharm Sci 47:139–151

    Article  CAS  PubMed  Google Scholar 

  • Dash P, Gendelman H, Roy U, Balkundi S, Alnouti Y, Mosley R, Gelbard H, McMillan J, Gorantla S, Poluektova L (2012) Long-acting nanoformulated antiretroviral therapy elicits potent antiretroviral and neuroprotective responses in HIV-1-infected humanized mice. AIDS 26:2135–2144

    Article  CAS  PubMed  Google Scholar 

  • Date A, Destache C (2013) A review of nanotechnological approaches for the prophylaxis of HIV/AIDS. Biomaterials 34:6202–6228

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Destache C, Belgum T, Goede M, Shibata A, Belshan M (2010) Antiretroviral release from poly(DL-lactide-coglycolide) nanoparticles in mice. J Antimicrob Chemother 65:2183–2187

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dhembre G, Moon R, Kshirsagar R (2011) A review on polymeric micellar nanocarriers. Int J Pharm Biol Sci 2:109–116

    CAS  Google Scholar 

  • Doktorovováa S, Araújob J, Garciab M, Rakovský E, Soutoa E (2010) Formulating fluticasone propionate in novel PEG-containing nanostructured lipid carriers (PEG-NLC). Colloids Surf B Biointerfaces 75:538–542

    Article  CAS  Google Scholar 

  • Dou H, Destache C, Morehead J, Mosley R, Boska M, Kingsley J, Gorantla S, Poluektova L, Nelson J, Chaubal M, Werling J, Kipp J, Rabinow B, Gendelman H (2006) Development of a macrophage-based nanoparticle platform for antiretroviral drug delivery. Blood 108:2827–2835

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dou H, Grotepas CB, McMillan J, Destache C, Chaubal M, Werling J, Kipp J, Rabinow B, Gendelman H (2009) Macrophage delivery of nanoformulated antiretroviral drug to the brain in a murine model of neuroAIDS. J Immunol 183:661–669

    Article  CAS  PubMed  Google Scholar 

  • Dusserre N, Lessard C, Paquette N, Perron S, Poulin L, Tremblay M, Beauchamp D, Désormeaux A, Bergeron M (1995) Encapsulation of foscarnet in liposomes modifies drug intracellular accumulation, in vitro anti-HIV-1 activity, tissue distribution and pharmacokinetics. AIDS 9:833–841

    Article  CAS  PubMed  Google Scholar 

  • Dutta T, Jain N (2007) Targeting potential and anti-HIV activity of lamivudine loaded mannosylated poly (propyleneimine) dendrimers. Biochim Biophys Acta, Gen Subj 1770:681–686

    Article  CAS  Google Scholar 

  • Dutta T, Garg M, Jain N (2008) Targeting of efavirenz loaded tuftsin conjugated poly (propyleneimine) dendrimers to HIV infected macrophages in vitro. Eur J Pharm Sci 34:181–189

    Article  CAS  PubMed  Google Scholar 

  • Fact sheet. UNAIDS. 2018. http://www.unaids.org/en/resources/fact-sheet.

  • Fiandra L, Colombo M, Mazzucchelli S, Santini B, Nebuloni M, Capetti A, Rizzardini G, Prosperi D, Corsi F (2015) Nanoformulation of antiretroviral drugs enhances their penetration across the blood brain barrier in mice. Nanomedicine 11:1387–1397

    Article  CAS  PubMed  Google Scholar 

  • Gonzalez-Scarano F, Martin-Garcia J (2005) The neuropathogenesis of AIDS. Nat Rev Immunol 5:69–81

    Article  CAS  PubMed  Google Scholar 

  • Greene W (2007) A history of AIDS: looking back to see ahead. Eur J Immunol 37:94–102

    Article  Google Scholar 

  • Gupta S, Kesarla R, Chotai N, Misra A, Omri A (2017) Systematic approach for the formulation and optimization of solid lipid nanoparticles of efavirenz by high pressure homogenization using design of experiments for brain targeting and enhanced bioavailability. Biomed Res Int 2017:5984014

    PubMed  PubMed Central  Google Scholar 

  • https://commons.wikimedia.org/HIV_Virion-en.png

  • Hu F, Jiang S, Du Y, Yuan H, Ye Y, Zeng S (2006) Preparation and characteristics of monostearin nanostructured lipid carriers. Int J Pharm 314:83–89

    Article  CAS  PubMed  Google Scholar 

  • Jain S, Gupta Y, Jain A, Saxena A, Khare P, Jain A (2009) Mannosylated gelatin nanoparticles bearing an anti-HIV drug didanosine for site-specific delivery. Nanomedicine 4:41–48

    Article  CAS  Google Scholar 

  • Jin S, Bi D, Wang J, Wang Y, Hu H, Deng Y (2005) Pharmacokinetics and tissue distribution of zidovudine in rats following intravenous administration of zidovudine myristate loaded liposomes. Pharmazie 60:840–843

    CAS  PubMed  Google Scholar 

  • Jindal S, Bachhav P, Anil B (2017) In situ hybrid nano drug delivery system (IHN-DDS) of antiretroviral drug for simultaneous targeting to multiple viral reservoirs: an in vivo proof of concept. Int J Pharm 521:196–203

    Article  CAS  PubMed  Google Scholar 

  • Johanson C, Stopa E, McMillan P (2011) The blood-cerebrospinal fluid barrier: structure and functional significance. Methods Mol Biol 686:101–131

    Article  CAS  PubMed  Google Scholar 

  • Joshy K, Sharma C (2012) Blood compatible nanostructured lipid carriers for the enhanced delivery of azidothymidine to brain. Adv Sci Lett 6:47–55

    Article  CAS  Google Scholar 

  • Kabanov A, Alakhov V (2002) Pluronic® block copolymers in drug delivery: from micellar nanocontainers to biological response modifiers. Crit Rev Ther Drug Carrier Syst 19:1–72

    Article  CAS  PubMed  Google Scholar 

  • Kandadi P, Syed M, Goparaboina S, Veerabrahma K (2011) Brain specific delivery of pegylated indinavir submicron lipid emulsions. Eur J Pharm Sci 42:423–432

    Article  CAS  PubMed  Google Scholar 

  • Kaur A, Jain S, Tiwary A (2008) Mannan-coated gelatin nanoparticles for sustained and targeted delivery of didanosine: in vitro and in vivo evaluation. Acta Pharm 58:61–74

    Article  CAS  PubMed  Google Scholar 

  • Koopmans P, Ellis R, Best B, Letendre S (2009) Should antiretroviral therapy for HIV infection be tailored for intracerebral penetration? Neth J Med 67:206–211

    CAS  PubMed  PubMed Central  Google Scholar 

  • Kramer-Hämmerle S, Rothenaigner I, Wolff H, Bell J, Brack-Werner R (2005) Cells of the central nervous system as targets and reservoirs of the human immunodeficiency virus. Virus Res 111:194–213

    Article  PubMed  CAS  Google Scholar 

  • Kuo Y, Su F (2007) Transport of stavudine, delavirdine, and saquinavir across the blood–brain barrier by polybutylcyanoacrylate, methylmethacrylate-sulfopropylmethacrylate, and solid lipid nanoparticles. Int J Pharm 340:143–152

    Article  CAS  PubMed  Google Scholar 

  • Mahajan S, Roy I, Xu G, Yong K, Ding H, Aalinkeel R, Reynolds J, Sykes D, Nair B, Lin E, Prasad P, Schwartz S (2010) Enhancing the delivery of antiretroviral drug “Saquinavir” across the blood brain barrier using nanoparticles. Curr HIV Res 8:396–404

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mahajan S, Law W, Aalinkeel R, Reynolds J, Nair B, Yong K, Roy I, Prasad P, Schwartz S (2012) Nanoparticle-mediated targeted delivery of antiretrovirals to the brain. Methods Enzymol 509:41–60

    Article  CAS  PubMed  Google Scholar 

  • Mahajan H, Mahajan M, Nerkar P, Agrawal A (2014) Nanoemulsion-based intranasal drug delivery system of saquinavir mesylate for brain targeting. Drug Deliv 21:148–154

    Article  CAS  PubMed  Google Scholar 

  • Mainardes R, Gremião M, Brunetti I, Fonseca L, Khalil N (2009) Zidovudine-loaded PLA and PLA–PEG blend nanoparticles: influence of polymer type on phagocytic uptake by polymorphonuclear cells. J Pharm Sci 98:257–267

    Article  CAS  PubMed  Google Scholar 

  • McGee B, Smith N, Aweeka F (2006) HIV pharmacology: barriers to the eradication of HIV from the CNS. HIV Clin Trials 7:142–153

    Article  PubMed  Google Scholar 

  • Miller S (2002) HIV life cycle and potential targets for drug activity. South Afr J HIV Med 7:102–103

    Google Scholar 

  • Morison L (2001) The global epidemiology of HIV/AIDS. Br Med Bull 58:7–18

    Article  CAS  PubMed  Google Scholar 

  • Nair M, Jayant R, Kaushik A, Sagar V (2016) Getting into the brain: potential of nanotechnology in the management of NeuroAIDS. Adv Drug Deliv Rev 103:202–217

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pardridge W (2002) Brain drug targeting: the future of brain drug development. J Clin Pathol 55(2):158

    Google Scholar 

  • Rao K, Ghorpade A, Labhasetwar V (2009) Targeting anti-HIV drugs to the CNS. Expert Opin Drug Deliv 6:771–784

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rautio J, Kumpulainen H, Heimbach T, Oliyai R, Oh D, Jarvinen T, Savolainen J (2008) Prodrugs: design and clinical applications. Nat Rev Drug Discov 7:255–269

    Article  CAS  PubMed  Google Scholar 

  • Rodriguez M, Kaushik A, Lapierre J, Dever S, El-Hage N, Nair M (2017a) Electro-magnetic nano-particle bound Beclin1 siRNA crosses the blood – brain barrier to attenuate the inflammatory effects of HIV-1 infection in vitro. J Neuroimm Pharmacol 12:120–132

    Article  Google Scholar 

  • Rodriguez M, Lapierre J, Ojha C, Kaushik A, Batrakova E, Kashanchi F, Dever S, Nair M, El-Hage N (2017b) Intranasal drug delivery of small interfering RNA targeting Beclin1 encapsulated with polyethylenimine (PEI) in mouse brain to achieve HIV attenuation. Nat Sci Rep 8:71–10

    Google Scholar 

  • Saiyed M, Gandhi N, Nair M (2010) Magnetic nanoformulation of azidothymidine 5′-triphosphate for targeted delivery across the blood–brain barrier. Int J Nanomedicine 5:157–166

    CAS  PubMed  PubMed Central  Google Scholar 

  • Shah L, Amiji M (2006) Intracellular delivery of saquinavir in biodegradable polymeric nanoparticles for HIV/AIDS. Pharm Res 23:2638–2645

    Article  CAS  PubMed  Google Scholar 

  • Sharp P, Hahn B (2012) Origins of HIV and the AIDS pandemic. Cold Spring Harb Perspect Med 1:a006841

    Google Scholar 

  • Shegokar R, Singh K (2011) Surface modified nevirapine nanosuspensions for viral reservoir targeting: in-vitro and in-vivo evaluation. Int J Pharm 421:341–352

    Article  CAS  PubMed  Google Scholar 

  • Shegokar R, Jansch M, Singh K, Muller R (2011) In vitro protein adsorption studies on nevirapine nanosuspensions for HIV/AIDS chemotherapy. Nanomed Nanotechnol Biol Med 7:333–340

    Article  CAS  Google Scholar 

  • Spitzenberger T, Heilman D, Diekmann C, Batrakova E, Kabanov A, Gendelman H, Elmquist W, Persidsky Y (2007) Novel delivery system enhances efficacy of antiretroviral therapy in animal model for HIV-1 encephalitis. J Cereb Blood Flow Metab 27:1033–1042

    Article  CAS  PubMed  Google Scholar 

  • Trkola A (2004) HIV-host interactions: vital to the virus and key to its inhibition. Curr Opin Microbiol 7:555–559

    Article  CAS  PubMed  Google Scholar 

  • Varatharajana L, Thomas S (2009) The transport of anti-HIV drugs across blood–CNS interfaces: summary of current knowledge and recommendations for further research. Antivir Res 82:A99–A109

    Article  CAS  Google Scholar 

  • Vinogradov S, Poluektova L, Makarov E, Gerson T, Senanayake M (2010) Nano-NRTIs: efficient inhibitors of HIV type-1 in macrophages with a reduced mitochondrial toxicity. Antivir Chem Chemother 21:1–14

    Article  CAS  PubMed  Google Scholar 

  • Vyas T, Shah L, Amiji M (2006) Nanoparticulate drug carriers for delivery of HIV/AIDS therapy to viral reservoir sites. Expert Opin Drug Deliv 3:613–628

    Article  CAS  PubMed  Google Scholar 

  • Wong H, Wu X, Bendayan R (2012) Nanotechnological advances for the delivery of CNS therapeutics. Adv Drug Deliv Rev 64:686–700

    Article  CAS  PubMed  Google Scholar 

  • Zaitseva M, Peden K, Golding H (2003) HIV coreceptors: role of structure, posttranslational modifications, and internalization in viral cell fusion and as targets for entry inhibitors. Biochim Biophys Acta 1614:51–61

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. SVKM’s Institute of Pharmacy, Dhule, Maharashtra, India

    Aarti Belgamwar

  2. Institute of Pharmaceutical Education and Research, Borgaon (Meghe), Wardha, Maharashtra, India

    Shagufta Khan

  3. Dr. Babasaheb Ambedkar Marathwada University, Aurangabad, Maharashtra, India

    Pramod Yeole

Authors
  1. Aarti Belgamwar
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Shagufta Khan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Pramod Yeole
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Nanobiotechnology Laboratory, Department of Biotechnology, SGB Amravati University, Amravati, Maharashtra, India, Department of Chemistry, Federal University of Piauí, Teresina, Piauí, Brazil

    Mahendra Rai

  2. Nanobiotechnology Laboratory, Department of Biotechnology, SGB Amravati University, Amravati, Maharashtra, India

    Alka Yadav

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Belgamwar, A., Khan, S., Yeole, P. (2019). Nanomedicines for Improved Antiretroviral Therapy in Neuro-AIDS. In: Rai, M., Yadav, A. (eds) Nanobiotechnology in Neurodegenerative Diseases. Springer, Cham. https://doi.org/10.1007/978-3-030-30930-5_10

Download citation

Publish with us

Policies and ethics

Search

Navigation