Efficacy of Novel Oral Formulations of α/β Arteether against Multidrug-Resistant Malaria in Mice

Abstract

Background: α/β arteether (AE), an effective artemisinin derivative, was developed as intramuscular injection for multidrug-resistant (MDR) and severe falciparum malaria, but intramuscular treatment has its own limitations and cannot be given to patients in rural areas where proper hospital facilities are not available and people are reluctant to take injections. Due to widespread occurrence of MDR strains of Plasmodiumfalciparum, an oral AE formulation is urgently needed to cure the malaria patients. Methods: Several AE formulations were prepared and tested orally in Swiss mice infected with MDR P. yoelii nigeriensis at a dose of 50 mg/kg/day for 5 days. The comparative antimalarial efficacy of eight different AE formulations was assessed at different time intervals in treated and control animals. Results: Three new AE formulations, namely AE F-2, F-10B and F-14, were found to have 100% curative antimalarial activity in an experimental model, as shown by survival of treated animals beyond 28 days, with no recrudescence of parasitemia being recorded. Another two formulations, AE F-8 and F-9B, produced 96–97% cure. Conclusion: Five α/β AE formulations (F-2, F-10B, F-8, F-9B and F-14) can be considered potential candidates for further drug development. AE F-14, a solid dosage form of AE prepared by completely removing oil and incorporating 0.2% cholesterol, is a new promising lead, even in pediatric malaria, which can reduce the neurotoxic potential of AE and other artemisinin derivatives.

Self-nanoemulsifying drug delivery systems (SNEDDS) for oral delivery of arteether: pharmacokinetics, toxicity and antimalarial activity in mice

“…The SNEDDS used in this study were well tolerated by the experimental mice and there was no abnormality seen in the behavior, food/water consumption and general activity of the animals throughout the treatment and post treatment period. 33 The anti-malarial prole of these formulations is given in Table 7.…”

“…Blood schizontocidal activity of F-1, F-2, F-3 and F-4 was assessed according to the method reported earlier with some modications. 55 F-1, F-2, F-3 and F-4 were administered once daily by the oral route, starting from the day of infection (day 0) and with continuing once daily administration for a total of 5 days. Thin blood smears were prepared from the tail vein of each animal on days 4, 7, 10, 14, 21, 24 and 28 in order to check the parasitaemia.…”

Nematodicidal Activity of Flubendazole and Its Reduced Metabolite on a Murine Model of <b><i>Trichinella spiralis </i></b>Infection

“…The characterization of the pharmacokinetic and/or pharmacodynamic patterns has been relevant to optimize drug use in the treatment of different bacterial and parasitic infections [1,2,3]. Benzimidazole-methylcarbamates (BZD) are broad-spectrum anthelmintic compounds widely used in human and veterinary medicine to control nematode, cestode and trematode infections [4].…”

Novel formulation and drug delivery strategies for the treatment of pediatric poverty-related diseases

“…a/b-Arteether (AE), an artemisinin derivative effective against MDR and severe falciparum malaria [139], is available as an intramuscular injection that can be painful and requires trained personnel, who are unavailable in rural areas, for administration. Tripathi et al developed eight oral oily formulations of AE and tested the effectiveness in mice infected with MDR Plasmodium yoelii nigeriensis [140]. Cure extents ranged between 96 and 100% with no parasitemia rebound after 4 weeks.…”