Intranasal artesunate-loaded nanostructured lipid carriers: A convenient alternative to parenteral formulations for the treatment of severe and cerebral malaria

Chinazom Agbo*, Timothy Ugwuanyi, Wilfred Ugwuoke, Christopher McConville, Anthony Attama, Kenneth Ofokansi

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Early treatment with parenteral antimalarials is key in preventing deaths and complications associated with severe and cerebral malaria. This can be challenging in 'hard-to-reach' areas in Africa where transit time to hospitals with facilities to administer drugs parenterally can be more than 6 h. Consequently, the World Health Organization has recommended the use of artesunate (ATS) suppositories for emergency treatment of patients, however, this treatment is only for children under 6 years. The intranasal route (INR) can provide a safe and effective alternative to parenteral and rectal routes for patients of all ages; thus, reducing delays to the initiation of treatment. Hence, we designed ATS-loaded nanostructured lipid carriers (NLCs) for intranasal administration. ATS-NLCs were formulated using varying concentrations of lipid matrices made up of solidified reverse micellar solutions (SRMS) comprising a 1:2 ratio of Phospholipon ® 90H and lipids (Softisan ® 154 or Compritol ®). ATS-NLCs were spherical, and the small sizes of ATS-NLCs obtained for some formulations (76.56 ± 1.04 nm) is an indication that ATS-NLCs can pass through the nasal mucosa and reach the brain or systemic circulation. Encapsulation efficiency of ATS in NLCs was ≥70% for all formulations. ATS-NLCs achieved up to 40% in vitro drug release in 1 h, while ex vivo permeation studies revealed that formulating ATS as NLCs enhanced permeation through pig nasal mucosa better than drug solution. Most importantly, the activity and reduction in parasitaemia [in mice infected with Plasmodium berghei ANKA in a murine cerebral malaria model] by ATS-NLCs administered through the INR (54.70%, 33.28%) was comparable to intramuscular administration (58.80%, 42.18%), respectively. Therefore, intranasal administration of NLCs of ATS has great potentials to serve as a satisfactory alternative to parenteral administration for the treatment of severe and cerebral malaria in both adults and children in remote areas of sub-Saharan Africa.
Original languageEnglish
Pages (from-to)224-236
Number of pages13
JournalJournal of Controlled Release
Volume334
Early online date22 Apr 2021
DOIs
Publication statusPublished - 10 Jun 2021

Keywords

  • Severe malaria
  • Cerebral malaria
  • Artesunate
  • Intranasal route
  • Nanostructured lipid carriers
  • Solidified reverse micellar solutions

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