title: A novel strategy for the treatment of chronic wounds based on the topical administration of rhEGF-loaded lipid nanoparticles: In vitro bioactivity and in vivo effectiveness in healing-impaired db/db mice.
abstract: Lipid nanoparticles are currently receiving increasing interest because they permit the topical administration of proteins, such as recombinant human epidermal growth factor (rhEGF), in a sustained and effective manner. Because chronic wounds have become a major healthcare burden, the topical administration of rhEGF-loaded lipid nanoparticles, namely solid lipid nanoparticles (SLN) and nanostructured lipid carries (NLC), appears to be an interesting and suitable strategy for the treatment of chronic wounds. Both rhEGF-loaded lipid nanoparticles were prepared through the emulsification-ultrasonication method; however, the NLC-rhEGF preparation did not require the use of any organic solvents. The characterisation of the nanoparticles (NP) revealed that the encapsulation efficiency (EE) of NLC-rhEGF was significantly greater than obtained with SLN-rhEGF. The in vitro experiments demonstrated that gamma sterilisation is a suitable process for the final sterilisation because no loss in activity was observed after the sterilisation process. In addition, the proliferation assays revealed that the bioactivity of the nanoformulations was even higher than that of free rhEGF. Finally, the effectiveness of the rhEGF-loaded lipid nanoparticles was assayed in a full-thickness wound model in db/db mice. The data demonstrated that four topical administrations of SLN-rhEGF and NLC-rhEGF significantly improved healing in terms of wound closure, restoration of the inflammatory process, and re-epithelisation grade. In addition, the data did not reveal any differences in the in vivo effectiveness between the different rhEGF-loaded lipid nanoparticles. Overall, these findings demonstrate the promising potential of rhEGF-loaded lipid nanoparticles, particularly NLC-rhEGF, for the promotion of faster and more effective healing and suggest their future application for the treatment of chronic wounds.
authors.affiliation: NanoBioCel Group, Laboratory of Pharmaceutics, School of Pharmacy, University of the Basque Country, Vitoria, Spain; Biomedical Research Networking Centre in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Vitoria, Spain.
authors.forename: Garazi
authors.initials: G
authors.lastname: Gainza
authors.affiliation: NanoBioCel Group, Laboratory of Pharmaceutics, School of Pharmacy, University of the Basque Country, Vitoria, Spain; Biomedical Research Networking Centre in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Vitoria, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Pastor
authors.affiliation: Hospital Universitario de Álava (HUA) Txagorritxu, Vitoria 01009, Spain.
authors.forename: José Javier
authors.initials: JJ
authors.lastname: Aguirre
authors.affiliation: Biopraxis Research AIE, Miñano 01510, Spain.
authors.forename: Silvia
authors.initials: S
authors.lastname: Villullas
authors.affiliation: NanoBioCel Group, Laboratory of Pharmaceutics, School of Pharmacy, University of the Basque Country, Vitoria, Spain; Biomedical Research Networking Centre in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Vitoria, Spain.
authors.forename: José Luis
authors.initials: JL
authors.lastname: Pedraz
authors.affiliation: NanoBioCel Group, Laboratory of Pharmaceutics, School of Pharmacy, University of the Basque Country, Vitoria, Spain; Biomedical Research Networking Centre in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Vitoria, Spain.
authors.forename: Rosa Maria
authors.initials: RM
authors.lastname: Hernandez
authors.affiliation: NanoBioCel Group, Laboratory of Pharmaceutics, School of Pharmacy, University of the Basque Country, Vitoria, Spain; Biomedical Research Networking Centre in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Vitoria, Spain. Electronic address: manoli.igartua@ehu.es.
authors.forename: Manoli
authors.initials: M
authors.lastname: Igartua
mesh_terms: D016475:3T3 Cells; D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D004337:Drug Carriers / Q000737:chemistry*; D004815:Epidermal Growth Factor / Q000008:administration & dosage* / Q000627:therapeutic use*; D006801:Humans; D008055:Lipids / Q000737:chemistry*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D004337:Drug Carriers; D008055:Lipids; D011994:Recombinant Proteins; D004815:Epidermal Growth Factor
keywords: Chronic wounds; EGF (epidermal growth factor); Lipid nanoparticles; NLC (nanostructured lipid carriers); SLN (solid lipid nanoparticles); Tissue engineering