Formulating Cod Liver Oil Nanoemulsions for Topical Application: A Multifactorial Study Linking Formulation Design to Physicochemical Stability, Oxidative Integrity and In Vitro Cytotoxicity

Abstract

Cod liver oil is a rich source of polyunsaturated fatty acids (PUFAs) but is highly susceptible to oxidative degradation, limiting its use in topical formulations. This study aimed to develop stable cod liver oil nanoemulsions for topical application and to evaluated the influence of surfactant ratio (lecithin/PEG-15 hydroxystearate: 2.5:1 and 1:1, w/w), emulsification method (ultrasonication or high-pressure homogenization), and vitamin E acetate supplementation on their physicochemical properties and oxidative stability. Eight nanoemulsions were characterized in terms of droplet size, polydispersity, ζ-potential, vitamin E acetate encapsulation efficiency, oxidative stability, film-forming capacity and cytocompatibility. Among the investigated formulations, F4 (2.5:1 lecithin/PEG-15 hydroxystearate, high-pressure homogenization, with vitamin E acetate) exhibited the most favorable characteristics, including a mean droplet size of 67.95 nm, ζ-potential of −63.12 mV and vitamin E acetate encapsulation efficiency of 32.59%. The formulation demonstrated good physicochemical stability under thermal, mechanical and photostability testing, improved oxidative stability, transient film-forming behavior with an initial occlusive effect, and no cytotoxicity toward human dermal fibroblasts. These findings indicate that nanoemulsion performance depends on the combined influence of formulation composition and processing conditions, with F4 representing a promising topical carrier for cod liver oil intended for interaction with the stratum corneum.