Skip to main content
SpringerLink
Log in

Modern Approaches in Nanomedicine for NeuroAIDS and CNS Drug Delivery

  • Chapter
  • First Online:
NanoBioMedicine

Abstract

NeuroAIDS is a neuropsychiatric disorder primarily caused by chronic human immunodeficiency virus (HIV). The most common neurological complications during NeuroAIDS are HAD (HIV-associated dementia) and HAND (HIV-associated neurocognitive disorder). HAART (highly active antiretroviral therapy) is a group of ARV (antiretroviral) drugs used to inhibit the key proteins involved in HIV replication. ARV drugs are extensively used to decrease the viral load and risk of opportunistic infections and to prolong survival of HIV-infected individuals. Significant advancement in antiretroviral (ARV) drugs has been achieved. However, the elimination of HIV from the CNS remains a difficult task. The complex structure of blood-brain barrier (BBB), high plasma protein binding, low patient compliance, and poor pharmacokinetics and biodistribution are the major limitations which restrict the effective concentration of drug to the CNS resulting in low efficacy of HAART in the CNS. Development of novel nanotechnology-based drug delivery methods for ARV drugs can increase the effectiveness of regimen with fewer side effects and better patient compliance which reduces financial load of healthcare system. The present article discusses about the nanotechnology-based approaches that can improve the delivery of ARV, called nano-ART. Nano-ART has excellent BBB permeability and improved pharmacokinetics and biodistribution that have significant clinical advantages to cure the CNS infection of HIV.

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

Access this chapter

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 219.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 279.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 279.99
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

Institutional subscriptions

Abbreviations

HIV:

Human immunodeficiency virus

HAND:

HIV-associated neurocognitive disorders

CNS:

Central nervous system

ARV:

Antiretroviral

ART:

Antiretroviral therapy

BBB:

Blood-brain barrier

HAD:

HIV-associated dementia

HAART:

Highly active antiretroviral therapy

SLN:

Solid lipid nanoparticles

MNP:

Magnetic nanoparticles

References

  • Alam MI, Beg S, Samad A, Baboota S, Kohli K, Ali J, Ahuja A, Akbar M (2010) Strategy for effective brain drug delivery. Eur J Pharm Sci 40(5):385–403

    Article  CAS  PubMed  Google Scholar 

  • Bain LE, Nkoke C, Noubiap JJN (2017) UNAIDS 90-90-90 targets to end the AIDS epidemic by 2020 are not realistic: comment on “Can the UNAIDS 90-90-90 target be achieved? A systematic analysis of national HIV treatment cascades”. BMJ Glob Health 2(2):e000227

    Article  PubMed  PubMed Central  Google Scholar 

  • Batrakova EV, Gendelman HE, Kabanov AV (2011) Cell-mediated drug delivery. Expert Opin Drug Deliv 8:415–433

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bondì ML, Di Gesù R, Craparo EF (2012) Lipid nanoparticles for drug targeting to the brain. Methods Enzymol 508:229–251

    Article  PubMed  CAS  Google Scholar 

  • Das MK, Sarma A, Chakraborty T (2016) Nano-ART and NeuroAIDS. Drug Deliv Transl Res 6(5):452–472

    Article  CAS  PubMed  Google Scholar 

  • Destache CJ, Belgum T, Goede M, Shibata A, Belshan MA (2010) Antiretroviral release from poly (DL-lactide-co-glycolide) nanoparticles in mice. J Antimicrob Chemother 65(10):2183–2187

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dou H, Grotepas CB, McMillan JM, Destache CJ, Chaubal M, Werling J (2009) Macrophage delivery of nanoformulated anti-retroviral drug to the brain in a murine model of Neuro-AIDS. J Immunol 183(1):661–669

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dutta T, Jain NK (2007) Targeting potential and anti-HIV activity of lamivudine loaded mannosylated poly (propyleneimine) dendrimer. BiophysActa 1770:681–686

    CAS  Google Scholar 

  • Geretti AM, Harrison L, Green H, Sabin C, Hill T, Fearnhill E, Pillay D, Dunn D, UK Collaborative Group on HIV Drug Resistance (2009) Effect of HIV-1 subtype on virologic and immunologic response to starting highly active antiretroviral therapy. Clin Infect Dis 48(9):1296–1305

    Article  CAS  PubMed  Google Scholar 

  • Gorantla S, Dou H, Boska M (2006) Quantitative magnetic resonance and SPECT imaging for macrophage tissue migration and nanoformulated drug delivery. J Leukoc Biol 80(5):1165–1174

    Article  CAS  PubMed  Google Scholar 

  • Häggblom A, Svedhem V, Singh K, Sönnerborg A, Neogi U (2016) Virological failure in patients with HIV-1 subtype C receiving antiretroviral therapy: an analysis of a prospective national cohort in Sweden. Lancet HIV 3(4):e166–e174

    Article  PubMed  PubMed Central  Google Scholar 

  • Heiati H, Tawashi R, Shivers RR, Phillips NC (1997) Solid lipid nanoparticles as drug carriers. I. Incorporation and retention of the lipophilic prodrug 3′-azido-3′-deoxythymidine palmitate. Int J Pharm 146(1):123–131

    Article  CAS  Google Scholar 

  • Hemelaar J (2012) The origin and diversity of the HIV-1 pandemic. Trends Mol Med 18(3):182–192

    Article  PubMed  Google Scholar 

  • Jayant RD, Atluri VSR, Agudelo M, Sagar V, Kaushik A, Nair M (2015) Sustained-release Nano-ART formulation for the treatment of Neuro-AIDS. Int J Nanomedicine 10:1077–1093

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kabanov AV, Gendelman HE (2007) Nanomedicine in the diagnosis and therapy of neurodegenerative disorders. Prog Polym Sci 32(8–9):1054–1082

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kaul M, Zheng J, Okamoto S, Gendelman HE, Lipton SA (2005) HIV-1 infection and AIDS: consequences for the central nervous system. Cell Death Differ 12:878–892

    Article  CAS  PubMed  Google Scholar 

  • Kaushik A, Jayant RD, Nair M (2016) Advancements in nano-enabled therapeutics for neuroHIV management. Int J Nanomedicine 11:4317–4325

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kaushik A, Jayant RD, Nair M (2018) Nanomedicine for neuroHIV/AIDS management. Nanomedicine (Lond) 13(7):669–673

    Article  CAS  Google Scholar 

  • Kim S, Scheerer S, Geyer MA, Howell SB (1990) Direct cerebrospinal fluid delivery of an antiretroviral agent using multivesicular liposomes. J Infect Dis 162:750–752

    Article  CAS  PubMed  Google Scholar 

  • Kumar S, Maurya VK, Dandu HR, Bhatt ML, Saxena SK (2018) Global perspective of novel therapeutic strategies for the management of NeuroAIDS. Biomol Concepts 9(1):33–42

    Article  CAS  PubMed  Google Scholar 

  • Kuo YC (2005) Loading efficiency of stavudine on polybutylcyanoacrylate and methylmethacrylate- sulfopropylmethacrylate copolymer nanoparticles. Int J Pharm 290:161–172

    Article  CAS  PubMed  Google Scholar 

  • Kuo Y-C, Su F-L (2007) Transport of stavudine, delavirdine, and saquinavir across the blood–brain barrier by polybutylcyanoacrylate, methylmethacrylate- sulfopropylmethacrylate, and solid lipid nanoparticles. Int J Pharm 340(1–2):143–152

    Article  CAS  PubMed  Google Scholar 

  • Lindl KA, Marks DR, Kolson DL, Jordan-Sciutto KL (2010) HIV-associated neurocognitive disorder: pathogenesis and therapeutic opportunities. J Neuroimmune Pharmacol 5(3):294–309

    Article  PubMed  PubMed Central  Google Scholar 

  • Mallipeddi R, Rohan LC (2010) Progress in antiretroviral drug delivery using nanotechnology. Int J Nanomedicine 5:533–547

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Maurya VK, Kumar S, Saxena SK (2018) Molecular mechanism of neuropathogenesis and current therapeutics for neuroAIDS. Res Rep 1:e1–e8

    Google Scholar 

  • McCombe JA, Noorbakhsh F, Buchholz C, Trew M, Power C (2009) NeuroAIDS: a watershed for mental health and nervous system disorders. J Psychiatry Neurosci 34(2):83–85

    PubMed  PubMed Central  Google Scholar 

  • Mehla R, Bivalkar-Mehla S, Zhang R, Handy I, Albrecht H, Giri S, Nagarkatti P, Nagarkatti M, Chauhan A (2010) Bryostatin modulates latent HIV-1 infection via PKC and AMPK signaling but inhibits acute infection in a receptor independent manner. PLoS One 5(6):e11160

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Mehta SK, Jindal N (2015) Tyloxapol niosomes as prospective drug delivery module for antiretroviral drug nevirapine. AAPS PharmSciTech 16(1):67–75

    Article  CAS  PubMed  Google Scholar 

  • Nair M, Guduru R, Liang P, Hong J, Sagar V, Khizroev S (2013) Externally controlled on-demand release of anti-HIV drug using magneto-electric nanoparticles as carriers. Nat Commun 4:1707

    Article  PubMed  CAS  Google Scholar 

  • Nair M, Jayant RD, 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 

  • Nicoli F, Gallerani E, Sforza F, Finessi V, Chachage M, Geldmacher C, Cafaro A, Ensoli B, Caputo A, Gavioli R (2018) The HIV-1 tat protein affects human CD4+ T-cell programming and activation, and favors the differentiation of naïve CD4+ T cells. AIDS 32(5):575–581

    CAS  PubMed  Google Scholar 

  • Nowacek A, Gendelman HE (2009) NanoART, neuroAIDS and CNS drug delivery. Nanomedicine (Lond) 4(5):557–574

    Article  CAS  Google Scholar 

  • Pant M, Garg P, Seth P (2012) Central nervous system infection by HIV-1: special emphasis to NeuroAIDS in India. Proc Natl Acad Sci India Sect B 82(1):81–94

    Article  Google Scholar 

  • Peng J, Wu Z, Qi X, Chen Y, Li X (2013) Dendrimers as potential therapeutic tools in HIV inhibition. Molecules 18:7912–7929

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rahimian P, He JJ (2017) HIV/neuroAIDS biomarkers. Prog Neurobiol 157:117–132

    Article  CAS  PubMed  Google Scholar 

  • Ramana LN, Sharma S, Sethuraman S, Ranga U, Krishnan UM (2014) Evaluation of chitosan nanoformulations as potent anti-HIV therapeutic systems. Biochim Biophys Acta 1840:476–484

    Article  CAS  PubMed  Google Scholar 

  • Rao KS, Reddy MK, Horning JL, Labhasetwar V (2008) TAT-conjugated nanoparticles for the CNS delivery of anti-HIV drugs. Biomaterials 29(33):4429–4438

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sagar V, Pilakka-Kanthikeel S, Pottathil R, Saxena SK, Nair M (2014) Towards nanomedicines for neuroAIDS. Rev Med Virol 24(2):103–124

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Saiyed ZM, Gandhi NH, Nair MP (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 

  • Sanmarti M, Ibáñez L, Huertas S, Badenes D, Dalmau D, Slevin M, Krupinski J, Popa-Wagner A, Jaen A (2014) HIV-associated neurocognitive disorders. J Mol Psychiatry 2(1):2

    Article  PubMed  PubMed Central  Google Scholar 

  • Saxena SK, Tiwari S, Nair MP (2012a) A global perspective on HIV/AIDS. Science 337(6096):798

    Article  CAS  PubMed  Google Scholar 

  • Saxena SK, Tiwari S, Nair MP (2012b) Nanotherapeutics: emerging competent technology in neuroAIDS and CNS drug delivery. Nanomedicine (Lond) 7(7):941–944

    Article  CAS  Google Scholar 

  • Schouten J, Cinque P, Gisslen M, Reiss P, Portegies P (2011) HIV-1 infection and cognitive impairment in the cART era: a review. AIDS 25(5):561–575

    Article  PubMed  Google Scholar 

  • Senanayake TH, Warren G, Wei X, Vinogradov SV (2013) Application of activated nucleoside analogs for the treatment of drug-resistant tumors by oral delivery of nanogel-drug conjugates. J Control Release 167:200–209

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Senanayake TH, Gorantla S, Makarov E, Lu Y, Warren G, Vinogradov SV (2015) Nanogel-conjugated reverse transcriptase inhibitors and their combinations as novel antiviral agents with increased efficacy against HIV-1 infection. Mol Pharm 12(12):4226–4236

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tauber SC, Staszewski O, Prinz M, Weis J, Nolte K, Bunkowski S, Brück W, Nau R (2016) HIV encephalopathy: glial activation and hippocampal neuronal apoptosis, but limited neural repair. HIV Med 17(2):143–151

    Article  CAS  PubMed  Google Scholar 

  • Varghese NM, Senthil V, Saxena SK (2018) Nanocarriers for brain specific delivery of anti-retro viral drugs: challenges and achievements. J Drug Target 26(3):195–207

    Google Scholar 

  • Vinogradov SV, Batrakova EV, Kabanov AV (2004) Nanogels for oligonucleotide delivery to the brain. Bioconjug Chem 15:50–60

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wong HL, Chattopadhyay N, Wu XY, Bendayan R (2010) Nanotechnology applications for improved delivery of antiretroviral drugs to the brain. Adv Drug Deliv Rev 18(62(4–5)):503–517

    Article  CAS  Google Scholar 

  • Xu Y, Kulkosky J, Acheampong E, Nunnari G, Sullivan J, Pomerantz RJ (2004) HIV-1-mediated apoptosis of neuronal cells: proximal molecular mechanisms of HIV-1-induced encephalopathy. Proc Natl Acad Sci U S A 101(18):7070–7075

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yilmaz A, Price RW, Gisslén M (2012) Antiretroviral drug treatment of CNSHIV-1 infection. J Antimicrob Chemother 67(2):299–311

    Article  CAS  PubMed  Google Scholar 

  • Zhang J, Li S, Li X (2009) Polymeric nano-assemblies as emerging delivery carriers for therapeutic applications: a review of recent patents. Recent Patents Nanotechnol 3:225–231

    Article  CAS  Google Scholar 

Download references

Acknowledgments

The authors are grateful to the Vice Chancellor, King George’s Medical University (KGMU), Lucknow, for the encouragement and support for this work. SK Saxena is also supported by CCRH, Government of India, and US NIH grants: R37DA025576 and R01MH085259. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Author information

Authors and Affiliations

  1. Centre for Advanced Research, Faculty of Medicine, King George’s Medical University (KGMU), Lucknow, India

    Shailendra K. Saxena, Vimal K. Maurya, Swatantra Kumar & Madan L. B. Bhatt

Authors
  1. Shailendra K. Saxena
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Vimal K. Maurya
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Swatantra Kumar
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Madan L. B. Bhatt
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Shailendra K. Saxena .

Editor information

Editors and Affiliations

  1. Centre for Advanced Research, King George’s Medical University, Lucknow, India

    Shailendra K. Saxena

  2. Amity University of Biotechnology, Amity University Haryana, Gurgaon, India

    S. M. Paul Khurana

Rights and permissions

Reprints and permissions

Copyright information

© 2020 Springer Nature Singapore Pte Ltd.

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Saxena, S.K., Maurya, V.K., Kumar, S., Bhatt, M.L.B. (2020). Modern Approaches in Nanomedicine for NeuroAIDS and CNS Drug Delivery. In: Saxena, S., Khurana, S. (eds) NanoBioMedicine. Springer, Singapore. https://doi.org/10.1007/978-981-32-9898-9_8

Download citation

Publish with us

Policies and ethics

Search

Navigation