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Formulation and evaluation of the antimalarial N-89 as a transdermal drug candidate. | LitMetric

Formulation and evaluation of the antimalarial N-89 as a transdermal drug candidate.

Parasitol Int

Division of International Infectious Diseases Control, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama 700-8530, Japan. Electronic address:

Published: April 2023

AI Article Synopsis

Article Abstract

The discovery of new effective and safe antimalarial drugs is mandatory. In this report, we formulate and evaluate transdermal (td) 1,2,6,7-tetraoxaspiro[7.11]nonadecane (N-89) using the Plasmodium berghei rodent malaria parasite in vivo model. The selected solvent for the ointment type of td N-89 was polyethylene glycol (PEG) [PEG400:PEG 4000 = 8:1 (v/w)]. We tested different application areas of 4, 6, and 8 cm on the shaved backs of mice. Pharmacokinetic (PK) analysis of N-89 parameters after a single 4 cm transdermal application revealed that the T was 2 h, the T was 1.9 h, and the AUC was 1951.1 ngh/mL. More than 10 ng/mL of plasma concentration was maintained for 12 h. The ED values for the 4, 6, and 8 cm application areas in a 4-day suppressive test were 18.9, 25.1, and 26.8 mg/kg, respectively. We additionally tested the cure effect of td N-89 in mice at a dose of 60 mg/kg, twice daily for 4 days at 0.2% parasitemia. Parasites disappeared following day 7 post-treatment in all td N-89 treated groups. Mice were cured without any parasite recurrence or dermal irritation. In conclusion, this study determined for the first time the PK parameters and effect of a new ointment type of td N-89. This suggests that transdermal treatment with N-89 is an effective and safe alternative route for the treatment of malaria, especially in children.

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Source
http://dx.doi.org/10.1016/j.parint.2022.102720DOI Listing

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