Epidermal growth factor (EGF) has been demonstrated to play a crucial role in the regeneration of skin. However, the topical application of the cytokine is limited by several key drawbacks, such as hair loss, chemical instability, need for supra-physiological (un-safe) dosages, photo-degradation as well as high cost; leading to patient non-compliance. The aim of the present study was to formulate a novel hybrid tunable delivery system in the form of a core–shell nanocapsules-based suspension. Nanocapsules were composed of cationic solid lipid nanoparticles (SLN)-based core and a customizable bi-layered shell structure produced by the layer-by-layer self-assembly of alternative coatings of anionic hyaluronan (HA) and cationic chitosan (CH). The resulted core–shell based nanocapsules were found to be physically stable, spherical, monodisperse, hydrophilic and cytocompatible in nature (<280 nm, cationic). The modulated release of low, safe and effective bioactive dosages of EGF is demonstrated. The system offers compartments for protein entrapment including the aqueous core and within the polyelectrolyte layers in the shell. To the best of knowledge, this is the first report describing the build-up of a tunable biopolymeric shell on a SLN core for the controlled/predictable delivery of bioactive recombinant human EGF with potential utility in skin regeneration and wound healing. © 2015 American Scientific Publishers. All rights reserved.