Exploring dosage forms for release of oleic acid as a mosquito larvicide

Abstract

Anopheles arabiensis is one of the primary malaria vectors in Southern Africa. Larviciding is a potential supplementary intervention that could help to reduce malaria transmission. Oleic acid, a non-toxic food additive, showed larvicidal activity against 3rd and 4th instar of the species corresponding to LC50 = 13  21 ppm and LC90 = 31  666 ppm after 48 h. This project explored controlled-release dosage form for oleic acid. Systems explored include microcapsules, films, oleogels, conventional emulsions and Pickering emulsions with zein, a plant protein derived from corn, as the excipient. Zein is insoluble in water but dissolves in aqueous ethanol. Such solutions provided the starting point for the preparation of the various dosage forms. Laboratory experiments suggest that Pickering emulsions represented the best delivery option. Pickering emulsions containing 30 wt.% oleic acid formulated with 3.0 wt.% zein particles as stabilisers showed the best formulation stability. Effective larviciding, with mortality approaching 100%, was achieved when this formulation was high shear mixed into water to a level of 250 ppm oleic acid. Unfortunately, it was not possible to dilute these Pickering emulsions using just mild agitation as would be necessary under real conditions. This is because stability was lost due to the pH of the natural water being too close to the isoelectric point of zein. This problem was avoided using oleic acid emulsion stabilised by sorbitan mono-oleate. However, in this case it took a long time for lethal oleic acid concentrations to develop some distance from the application point. This delay is attributed to the low solubility of oleic acid monomers and the diffusion-limited transport of aggregates forming in water. In conclusion, the study highlights the potential of using zein for the controlled release of oleic acid as a mosquito larvicide in emulsified form with oleic acid.