Recombinant Human Epidermal Growth Factor/Quatsome Nanoconjugates: A Robust Topical Delivery System for Complex Wound Healing

A multitude of microparticles and nanoparticles is developed to improve the delivery of different small drugs and large biomolecules, which are subject to several hindering biological barriers that limit their optimal biodistribution and therapeutic effects. Here, a soft, reliable, and scalable method based on compressed CO2 is reported for obtaining nanoconjugates of recombinant human epidermal growth factor and nanovesicles called quatsomes, where the latter consists of cholesterol and cetyltrimethylammonium bromide. These nanoconjugates exhibit appropriate values of the major critical quality attributes of colloidal nanomedicines, such as controlled and narrow nanoscopic particle size distribution (which play important roles in determining their stability), drug loading, drug release, drug protection, targeting ability, and bioactivity. Also, they exhibit a dual action by 1) inbuilt antimicrobial activity preventing infections and 2) promoting regeneration of granulation tissue and re‐epithelialization with complete closure of complex wounds. Therefore, such nanoconjugates are a potential nanomedicine for the topical treatment of complex wounds, particularly diabetic foot ulcers and venous leg ulcers.L.F.‐T and H.S. contributed equally to this work. This work was funded by the Spanish Ministry/FEDER project MOTHER MAT2016–80826‐R; the Networking Research Center on Bioengineering, Biomaterials, and Nanomedicine (CIBER‐BBN); the Generalitat de Catalunya (2017SGR918); and the Spanish Ministry of Economy and Competitiveness by the Severo Ochoa FUNFUTURE (CEX2019‐000917‐S) Excellence Centre distinction. This work was also co‐financed by the European Union through FEDER project NANONAFRES (COMRDI15‐1‐0023). The authors thank Milagros Font and Yenay Diaz from CIGB for technical assistance. The authors also thank the Industrial Doctorates Plan of Agaur‐Generalitat de Catalunya (2018 DI 057). Some figures of this work were created using Servier Medical Art templates, which are licensed under a Creative Commons Attribution 3.0 Unported License.Peer reviewe