The topical administration of rhEGF-loaded nanostructured lipid carriers (rhEGF-NLC) improves healing in a porcine full-thickness excisional wound model

Gainza, Garazi; Bonafonte, Diego Celdrán; Moreno, Beatriz; Aguirre, José Antonio Cadiñanos; Gutiérrez, Francisco Borja; Villullas, Silvia; Pedraz, José Luís; Igartua, Manoli; Hernández, Rosa María

doi:10.1016/j.jconrel.2014.10.033

Cited by 99 publications

(52 citation statements)

References 35 publications

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“…The administration of growth factors, such as epidermal growth 25 factor (EGF), to accelerate wound healing has been extensively 26 described (Choi et al, 2008;Chu et al, 2010;Gainza et al, 2013;27 Hardwicke et al, 2008;Hori et al, 2007;Johnson and Wang, 2013), 28 however, topical delivery of EGF is severely limited by its high 29 molecular weight, hydrophilicity and, above all, its short half life at 30 the wound site (Al Haushey et al, 2010;Choi et al, 2012;31 Ulubayram et al, 2001). To address these shortcomings, the nano-32 encapsulation of growth factors, like EGF, may enhance their 33 stability at the wound and may allow their controlled release, 34 thereby optimising efficacy.…”

mentioning

confidence: 99%

Development and in vitro evaluation of lipid nanoparticle-based dressings for topical treatment of chronic wounds

Gainza

Chu

Guy

et al. 2015

International Journal of Pharmaceutics

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This research addresses the development and in vitro evaluation of lipid nanoparticle (NP)-based dressings to optimize the delivery of human recombinant epidermal growth factor (rhEGF) for the topical treatment of chronic wounds. The systems investigated were rhEGF-loaded solid lipid nanoparticles (rhEGF-SLN) and rhEGF-loaded nanostructured lipid carriers (rhEGF-NLC) formulated in wound dressings comprising either semi-solid hydrogels or fibrin-based solid scaffolds. Following detailed characterisation of the NP, in vitro diffusion cell experiments (coupled with dermatopharmacokinetic measurements), together with confocal microscopic imaging, conducted on both intact skin samples, and those from which the barrier (the stratum corneum) had been removed, revealed that (a) the particles remained essentially superficially located for at least up to 48h post-application, (b) rhEGF released on the surface of intact skin was unable to penetrate to the deeper, viable layers, and (c) sustained release of growth factor from the NP "drug reservoirs" into barrier-compromised skin was observed. There were no significant differences between the in vitro performance of rhEGF-SLN and rhEGF-NLC, irrespective of the formulation employed. It is concluded that, because of their potentially longer-term stability, the fibrin-based scaffolds may be the most suitable approach to formulate rhEGF-loaded lipid nanoparticles.

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mentioning

confidence: 99%

Development and in vitro evaluation of lipid nanoparticle-based dressings for topical treatment of chronic wounds

Gainza

Chu

Guy

et al. 2015

International Journal of Pharmaceutics

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“…Once the epithelial barrier has been re-established, remodelling of the granulation tissue concomitant with the deposition of cross-linked collagen fibres is key events in the course of oral mucosa healing (Weinreb & Nemcovsky, 2015). Comparably to previous studies, the significant production of hypercellular granulation tissue (Kondo, Niiyama, Yu, & Kuroyanagi, 2012) at 8 days as well as the substantial deposition of highly organized collagen (Gainza et al, 2015) at 16 days illustrates herein the faster healing in rhEGF-treated sites, particularly with the 1 and 10 μg/g regimen at the opposite of the 50 μg/g concentration. Through the activation of mitogen-activated protein kinase-dependent pathways (Smith et al, 2009), not only EGF stimulates gingival fibroblasts to remove fibrin clot (Chiquet, Katsaros, & Kletsas, 2015), but also activates matrix metalloproteins, major ECM-proteolytic enzymes involved in the healing of human acute gingival wounds (Smith et al, 2009).…”

Section: Discussionmentioning

confidence: 83%

“…A total of fourteen dogs were employed to discriminate the dose‐dependent effect of rhEGF on oral wound repair. Considering the paucity of the data for the oral mucosa (Kim et al., ), three concentrations were selected in accordance with the literature addressing the treatment of skin wounds in humans (Brown et al., ; Fernández‐Montequín et al., ; Martí‐Carvajal et al., ; Wang, Ma, & Chai, ) or animals (Gainza et al., ; Hong et al., ) with rhEGF. Then, rhEGF incorporated in an ointment vehicle was tested in a discriminating pre‐clinical model.…”

Section: Discussionmentioning

confidence: 99%

“…Inflammatory cells secrete essential cytokine and growth factors necessary for angiogenesis and stromal cell migration (Eming, Krieg, & Davidson, 2007). With regard to a recent report demonstrating a substantial increase in vascular endothelial growth factor (VEGF) synthesis by human gingival fibroblasts exposed to EGF in vitro (Pansani et al, 2017), the elevated neovascularization EFG1 and EGF10 is not a surprising finding and strongly suggests the ability of rhEGF to promote oral mucosa wound healing by facilitating angiogenesis in addition to an earlier resolution of inflammation (Gainza et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

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Healing kinetics of oral soft tissue wounds treated with recombinant epidermal growth factor: Translation from a canine model

Amara

Thoma

Schwarz

et al. 2018

J Clinic Periodontology

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Objective To test whether or not topically administered recombinant human epidermal growth factor (rhEGF) accelerates the early healing phase of oral soft tissue wounds. Methods One day following the creation of palatal defects (n = 6/animal), 14 dogs were allocated to one of the following five groups: spontaneous healing (SH), vehicle ointment (V), vehicle ointment + rhEGF at concentrations of 1 μg/g (EGF1), 10 μg/g (EGF10) or 50 μg/g (EGF50). Topical administration of ointments was repeated twice per day until sacrifice at days 8 and 16. Wound area was clinically monitored. Keratinocytes proliferation (Ki67‐immunolabelling), inflammatory response (IR) and areas of collagen (C) and granulation tissue (GT) were histologically measured. Kruskal–Wallis test with Dunnett correction was used for multiple group statistical comparisons. Results Clinically, in comparison with SH, a significantly smaller wound area was observed in groups EGF1 and EGF10 at day 8 (p < 0.05). At day 16, wound closure reached 97.8% in group EGF1 compared to 83.2% in group SH, albeit no statistically different. Histologically, at day 8, significantly more GT was observed in group EGF10 compared to all other groups (p < 0.05). At day 16, in addition to a higher Ki67‐immunolabelling, groups EGF1 and EGF10 demonstrated a significant decrease in GT and IR with more deposition of C compared to the other groups (p < 0.05). Conclusion Application of rhEGF enhanced the early healing of acute oral soft tissue wounds compared to SH, predominantly at concentrations of 1 and 10 μg/g.

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“…Solid lipid nanoparticles have been evaluated for their potential to prolong opioids release for pain reduction in severe skin wounds [39]. Recombinant human epidermal growth factor-(rhEGF-) loaded nanostructured lipid carriers can present an important alternative in the treatment of chronic wounds since this formulation has been reported to improve the wound healing quality expressed in terms of number of arranged microvasculature, fibroblast migration and proliferation, collagen deposition, and evolution of the inflammatory response [40].…”

Section: Nanoparticles/micelles/lipidsmentioning

confidence: 99%

A Review of Injectable and Implantable Biomaterials for Treatment and Repair of Soft Tissues in Wound Healing

Chou

Gunaseelan

Kiellani

et al. 2017

Journal of Nanotechnology

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The two major topics concerning the development of nanomedicine are drug delivery and tissue engineering. With the advance in nanotechnology, scientists and engineers now have the ability to fabricate functional drug carriers and/or biomaterials that deliver and release drugs locally as well as promote tissue regeneration. In this short review, we address the use of nanotechnology in the fabrication of biomaterials (i.e., nanoparticles and nanofibers) and their therapeutic function in wound healing as dressing materials. Furthermore, we discuss the use of surface nanofeatures to regulate cell adhesion, migration, proliferation, and differentiation, which is a crucial step in wound healing associated with tissue regeneration. Given that nanotechnology-based biomaterials exhibit superior pharmaceutical performance as compared to the traditional medicine, this short review provides current status and future directions of how nanotechnology is and will be used in biomedical field, especially in wound healing.

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The topical administration of rhEGF-loaded nanostructured lipid carriers (rhEGF-NLC) improves healing in a porcine full-thickness excisional wound model

Cited by 99 publications

References 35 publications

Development and in vitro evaluation of lipid nanoparticle-based dressings for topical treatment of chronic wounds

Development and in vitro evaluation of lipid nanoparticle-based dressings for topical treatment of chronic wounds

Healing kinetics of oral soft tissue wounds treated with recombinant epidermal growth factor: Translation from a canine model

A Review of Injectable and Implantable Biomaterials for Treatment and Repair of Soft Tissues in Wound Healing

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