Primaquine and chloroquine nano-sized solid dispersion-loaded dissolving microarray patches for the improved treatment of malaria caused by Plasmodium vivax
Malaria is a global parasitic infection that leads to substantial illness and death. The most commonly-used drugs for treatment of malaria vivax are primaquine and chloroquine, but they have limitations, such as poor adherence due to frequent oral administration and gastrointestinal side effects. To overcome these limitations, we have developed nano-sized solid dispersion-based dissolving microarray patches (MAPs) for the intradermal delivery of these drugs. In vitro testing showed that these systems can deliver to skin and receiver compartment up to ≈60% of the payload for CQ-based dissolving MAPs and a total of ≈42% of drug loading for PQ-based dissolving MAPs. MAPs also displayed acceptable biocompatibility in cell tests. Pharmacokinetic studies in rats showed that dissolving MAPs could deliver sustained plasma levels of both PQ and CQ for over 7 days. Efficacy studies in a murine model for malaria showed that mice treated with PQ-MAPs and CQ-MAPs had reduced parasitaemia by up to 99.2%. This pharmaceutical approach may revolutionise malaria vivax treatment, especially in developing countries where the disease is endemic. The development of these dissolving MAPs may overcome issues associated with current pharmacotherapy and improve patient outcomes.
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Materials
Primaquine biphosphate (PQ) with a purity of 98% was obtained from Sigma Aldrich (Dorset, UK). Chloroquine diphosphate salt (CQ) with a purity of 98% was acquired from Alfa Aesar (Lancashire, UK). The internal standard, ketoconazole, was purchased from Sigma-Aldrich (St. Louis, MO, USA). Ethyl acetate, the deproteinising agent, was sourced from Fisher Scientific (Loughborough, UK). Soluplus® (a poly(N-vinyl caprolactam)–poly(vinyl acetate)–poly(ethylene glycol) graft copolymer) obtained from BASF (Ludwigshafen, Germany), and PVP 90 kDa (Plasdone™ K-29/32) obtained from Ashland (Kidderminster, UK) were also utilised. Other chemicals and reagents were purchased from Sigma-Aldrich (Dorset, UK).
Qonita Kurnia Anjani, Fabiana Volpe-Zanutto, Khuriah Abdul Hamid, Akmal Hidayat Bin Sabri, Natalia Moreno-Castellano, Xiomara A. Gaitán, Juliana Calit, Daniel Y. Bargieri, Ryan F. Donnelly,
Primaquine and chloroquine nano-sized solid dispersion-loaded dissolving microarray patches for the improved treatment of malaria caused by Plasmodium vivax,
Journal of Controlled Release,
Volume 361,
2023,
Pages 385-401,
ISSN 0168-3659,
https://doi.org/10.1016/j.jconrel.2023.08.009.
See also our article on World Malaria Day
