Orally Administrable Therapeutic Synthetic Nanoparticle for Zika Virus

Bapurao Surnar, Mohammad Z. Kamran, Anuj S. Shah, Uttara Basu, Nagesh Kolishetti, Sapna Deo, Dushyantha T. Jayaweera, Sylvia Daunert, Shanta Dhar

Research output: Contribution to journalArticle

Abstract

The spread of Zika virus (ZIKV) infection across the USA and various countries in the last three years will not only have a direct impact on the U.S. health care system but has caused international concerns as well. The ultimate impact of ZIKV infection remains to be understood. Currently, there are no therapeutic or vaccine options available to protect those infected by ZIKV. The drug ivermectin (IVM) was found to be a viable agent for the prevention of transmission of ZIKV. Ivermectin is unstable in the presence of water and does not remain in adequate concentration in the human bloodstream to be effective in treatment for ZIKV. Biodegradable nanoparticles would aid in the delivery of ivermectin by providing a high enough concentration of drug and ensuring the drug is gradually released to maintain an appropriate level in the body. The overall goal of this study was to develop and optimize an orally administrable nanoformulation of IVM which can circulate in the blood for a long period for efficient delivery. To achieve the goal, we synthesized and optimized a synthetic nanoformulation of IVM for oral use which can cross the intestinal epithelial barrier to enter the bloodstream. Our studies documented that when delivered with the synthetic nanoparticle (NP), IVM can be accumulated in the blood at a higher concentration and preliminary studies highlighted that NP delivered IVM has the ability to target nonstructural 1 protein of ZIKV. For potential clinical relevance, long-term storable formulation of IVM-nanoparticle in dry powder state for inclusion in a capsule form and cryoprotectant containing frozen forms revealed promising findings. Further, our preliminary in vitro studies documented that ivermectin crosses the placental barrier, thus making it unsafe for the pregnant ZIKV population, whereas the ivermectin-loaded nanoparticle did not show any significant placental barrier crossing, thus indicating its potential suitability for such population. We envision that this work will fill a great unmet need by developing safer and more effective therapies for the treatment of viral infections, including ZIKV.

Original languageEnglish (US)
Pages (from-to)11034-11048
Number of pages15
JournalACS Nano
Volume13
Issue number10
DOIs
StatePublished - Oct 22 2019

Fingerprint

Ivermectin
viruses
Viruses
Nanoparticles
nanoparticles
infectious diseases
drugs
blood
delivery
Blood
vaccines
Vaccines
Pharmaceutical Preparations
capsules
Health care
health
therapy
Powders
Capsules
inclusions

Keywords

  • dry formulation
  • epithelial crossing
  • Fc receptor
  • oral delivery
  • placental barrier
  • viral disease

ASJC Scopus subject areas

  • Materials Science(all)
  • Engineering(all)
  • Physics and Astronomy(all)

Cite this

Surnar, B., Kamran, M. Z., Shah, A. S., Basu, U., Kolishetti, N., Deo, S., ... Dhar, S. (2019). Orally Administrable Therapeutic Synthetic Nanoparticle for Zika Virus. ACS Nano, 13(10), 11034-11048. https://doi.org/10.1021/acsnano.9b02807

Orally Administrable Therapeutic Synthetic Nanoparticle for Zika Virus. / Surnar, Bapurao; Kamran, Mohammad Z.; Shah, Anuj S.; Basu, Uttara; Kolishetti, Nagesh; Deo, Sapna; Jayaweera, Dushyantha T.; Daunert, Sylvia; Dhar, Shanta.

In: ACS Nano, Vol. 13, No. 10, 22.10.2019, p. 11034-11048.

Research output: Contribution to journalArticle

Surnar B, Kamran MZ, Shah AS, Basu U, Kolishetti N, Deo S et al. Orally Administrable Therapeutic Synthetic Nanoparticle for Zika Virus. ACS Nano. 2019 Oct 22;13(10):11034-11048. https://doi.org/10.1021/acsnano.9b02807
Surnar, Bapurao ; Kamran, Mohammad Z. ; Shah, Anuj S. ; Basu, Uttara ; Kolishetti, Nagesh ; Deo, Sapna ; Jayaweera, Dushyantha T. ; Daunert, Sylvia ; Dhar, Shanta. / Orally Administrable Therapeutic Synthetic Nanoparticle for Zika Virus. In: ACS Nano. 2019 ; Vol. 13, No. 10. pp. 11034-11048.
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