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The study aimed to develop a patient-friendly acyclovir gel with improved efficacy in viral mouth infections, in response to patients' need for an intraoral acyclovir product. Acyclovir was loaded in lipid nanocapsules in gel form, and formulae were evaluated for oromucosal delivery. Lipid nanocapsules were prepared by the phase inversion method. Formulae were optimized to achieve maximum acyclovir entrapment and minimum acyclovir precipitation. Colloidal properties, and pharmaceutical performance indicators were assessed. Drug-loaded lipid nanocapsules were in the nanorange (39–120 nm), PdI (0.03–0.2), negative zeta potential, and entrapment efficiency (33–64%). Acyclovir (0.3% w/w) lipid nanocapsules gels were prepared using hydroxyethylcellulose (3% w/w). Resulting gel attributes were considered suitable.Lipid nanocapsules gels (0.3% w/w) showed enhanced Ex vivo acyclovir permeation across, and comparable retention in chicken pouch membrane compared to the 5% marketed cream despite lower drug content. The data provides basis for future exploration of lipid nanocapsules as carrier for transmucosal delivery of acyclovir; the enhanced acyclovir retention in chicken pouch membrane, compared to controls, suggests suitability of lipid nanocapsules for drug delivery to the viral lesion within the buccal membrane.