Achyrocline satureioides (Lam.) DC (Asteraceae) Extract-Loaded Nanoemulsions as a Promising Topical Wound Healing Delivery System: In Vitro Assessments in Human Keratinocytes (HaCaT) and HET-CAM Irritant Potential

Abstract

Achyrocline satureioides (Lam.) DC Asteraceae extracts (ASEs) have been investigated for the treatment of various skin disorders. This study reports the effects of ASE-loaded nanoemulsions (NEASE) on the cellular viability, death by necrosis, and migration of immortalized human keratinocytes (HaCaT cell line), as well as the irritant potential through the hen’s egg chorioallantoic membrane test (HET-CAM). NEASE exhibited a polydispersity index above 0.12, with a droplet size of 300 nm, ζ-potential of −40 mV, and content of flavonoids close to 1 mg/mL. No cytotoxicity of the ASE was observed on HaCaT by MTT assay (up to 10 µg/mL). A significant increase of HaCaT viability was observed to NEASE (up to 5 μg/mL of flavonoids), compared to treatment with the ASE. The necrosis death evaluation demonstrated that only NEASE did not lead to cell death at all the tested concentrations. The scratch assay demonstrated that NEASE was able to increase the cell migration at low flavonoid concentrations. Finally, the HET-CAM test proved the non-irritative potential of NEASE. Overall, the results indicate the potential of the proposed formulations for topical use in wound healing, in view of their promising effects on proliferation and migration in keratinocytes, combined with an indication of the absence of cytotoxicity and non-irritating potential.

Effect of Hydrogel Containing Achyrocline satureioides (Asteraceae) Extract–Loaded Nanoemulsions on Wound Healing Activity

“…Overall, the results are consistent with those observed for nanoemulsions prior to thickening with Carbopol ® Ultred. Thus, we demonstrated that under the conditions employed in this study, hydrogels containing nanoemulsions with A. satureioides extract maintained the evaluated parameters and are consistent with our previous study [13].…”

“…We recently demonstrated the potential of nanoemulsions containing the A. satureioides extract for topical use in wound healing. They presented promising effects on in vitro cell proliferation and keratinocyte migration, combined with an indication for the absence of cytotoxicity and non-irritating potential [13]. For topical application, the low viscosity of nanoemulsions is a concern, and the design of a semisolid formulation is an important consideration [15][16][17].…”

“…Considering the potential of A. satureioides extract as a wound healing agent and the low aqueous solubility of the flavonoid aglycones quercetin (QCT), luteolin (LUT), and 3-O-methylquercetin (3MQ) [8,11,12], our research group has addressed the feasibility of preparing nanoemulsions containing A. satureioides extract [13]. This delivery system features a small droplet size, which may help to overcome the skin barrier, and presents a high drug loading capacity and suitable properties for topical use [14].…”

A Review of Wound Healing Mechanisms of Natural Products in Keratinocyte Cells

“…This plant contains quercetin, luteolin and 3-O-methylquercetin (Figure 5). 29 The results showed a significant increase in the viability of HaCaT cells on ASE-loaded nanoemulsions (NEASE) (up to 5 μg/mL of flavonoids). Preliminary tests showed that NEASE was able to increase cell migration at low flavonoid concentrations.…”

The potential of functionalized dressing releasing flavonoids facilitates scar-free healing

“…In chronic deep second degree burns infected with Pseudomonas aeruginosa , catechin-loaded nanocollagen dressings exhibited antibacterial and pro-angiogenic properties, and regeneration of skin appendages and orderly collagen tissue alignment were seen, which may be the result of selective modulation of TGF-β1 and TGF-β3 by catechins ( 146 ). One study combined flavonoids into lipid nanoemulsions, which increased the viability of keratin-forming cells and their ability to migrate to wounds, accelerating scar-free skin regeneration ( 147 ). In a rat wound model, adding isoflavone glycosides to the nanoemulsion increased keratinocyte viability up to concentrations of 0.5 μg/mL.…”