Encapsulation of OZ439 into Nanoparticles for Supersaturated Drug Release in Oral Malaria Therapy

Hoang D. Lu, Kurt D. Ristroph, Ellen L.K. Dobrijevic, Jie Feng, Simon A. McManus, Yingyue Zhang, William D. Mulhearn, Hanu Ramachandruni, Anil Patel, Robert K. Prud'Homme

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

Malaria poses a major burden on human health and is becoming increasingly difficult to treat due to the development of antimalarial drug resistance. The resistance issue is further exacerbated by a lack of patient adherence to multi-day dosing regimens. This situation motivates the development of new antimalarial treatments that are less susceptible to the development of resistance. We have applied Flash NanoPrecipitation (FNP), a polymer-directed self-assembly process, to form stable, water-dispersible nanoparticles (NPs) of 50-400 nm in size containing OZ439, a poorly orally bioavailable but promising candidate for single-dose malaria treatment developed by Medicines for Malaria Venture (MMV). During the FNP process, a hydrophobic OZ439 oleate ion paired complex was formed and was encapsulated into NPs. Lyophilization conditions for the NP suspension were optimized to produce a dry powder. The in vitro release rates of OZ439 encapsulated in this powder were determined in biorelevant media and compared with the release rates of the unencapsulated drug. The OZ439 NPs exhibit a sustained release profile and several-fold higher release concentrations compared to that of the unencapsulated drug. In addition, XRD suggests the drug was stabilized into an amorphous form within the NPs, which may explain the improvement in dissolution kinetics. Formulating OZ439 into NPs in this way may be an important step toward developing a single-dose oral malaria therapeutic, and offers the possibility of reducing the amount of drug required per patient, lowering delivery costs, and improving dosing compliance.

Original languageEnglish (US)
Pages (from-to)970-979
Number of pages10
JournalACS Infectious Diseases
Volume4
Issue number6
DOIs
StatePublished - Jun 8 2018

All Science Journal Classification (ASJC) codes

  • Infectious Diseases

Keywords

  • drug delivery
  • hydrophobic ion pairing
  • malaria
  • nanocarrier
  • oral therapeutic

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    Lu, H. D., Ristroph, K. D., Dobrijevic, E. L. K., Feng, J., McManus, S. A., Zhang, Y., Mulhearn, W. D., Ramachandruni, H., Patel, A., & Prud'Homme, R. K. (2018). Encapsulation of OZ439 into Nanoparticles for Supersaturated Drug Release in Oral Malaria Therapy. ACS Infectious Diseases, 4(6), 970-979. https://doi.org/10.1021/acsinfecdis.7b00278