Thermoresponsive Hydrogel Containing Viscum album Extract for Topic and Transdermal Use: Development, Stability and Cytotoxicity Activity

Abstract

Viscum album L. (Santalaceae), also known as European mistletoe, is a semi-parasitic plant that grows on different host trees. Our group recently demonstrated the antitumoral activity of ethanolic V. album extracts in vitro, depending on the dose and the host tree, V. album ssp abietis from Abies alba being the most active extract. The goal of this work focused on the development of a new topical formulation containing V. album extracts, evaluation of in vitro toxicity and ex vivo skin permeation assays. The Poloxamer 407 hydrogel containing 5% of dry (VA_DEH) or aqueous (VA_AEH) extract presented dermal compatible pH and microbiological stability for 180 days. The hydrogels flow curve presented a non-linear relation, characteristic of non-Newtonian fluids, and the mean viscosity for the VA_DEH and VA_AEH was 372.5 ± 7.78 and 331.0 ± 2.83 Pa.s, respectively, being statistically different (Welch’s t test; p < 0.01). Additionally, WST-1 in vitro assays revealed a dose-dependent toxicity for both formulations and VA_DEH presented a higher activity than the VA_AEH. The promising cytotoxic potential of VA_DEH lead to the ex vivo skin permeation assay with 2.73 ± 0.19 µg/cm2 of chlorogenic acid, which permeated at 8 h, showing a transdermal potential. These in vitro results support the idea that VA_DEH is a novel promising candidate for mistletoe therapy. Therefore, further in vivo and pre-clinical experiments should be performed to evaluate the safety and efficacy of this new dermic delivery system.

Assessment of the Anti-Inflammatory, Antibacterial and Anti-Aging Properties and Possible Use on the Skin of Hydrogels Containing Epilobium angustifolium L. Extracts

“…Therefore, our study identified the total pool of polyphenols accumulated in the skin. Many authors confirm the accumulation of polyphenols in of the skin (Martimestres et al, 2007;Alonso et al, 2014Alonso et al, , 2015Batista et al, 2021). The difference between the intensity of C-H bonds of the skin treated of the HEas and control sample was observed.…”

“…The composition of the formulation is a significant factor. The results of our research on the penetration of phenolic acids was likely to be exerted by the moisturizing ingredient of the preparation, such as propylene glycol, which enhance membrane permeability by acting as an absorption promoter (Ratz-Łyko et al, 2015;Batista et al, 2021). Greater delivery of the active substance to the skin increases the effect of cosmetic and dermatological preparations.…”

“…For example, Žilius et al showed the high permeation of phenolic acids, such as coumaric, caffeic, and ferulic, from a hydrogel containing a propolis extract (Žilius et al, 2013). On the other hand, in other studies the penetration of chlorogenic acid from the hydrogel containing 5% (w/w) coffee extract (Bertges et al, 2020) and from the hydrogel containing 5% (w/w) Viscum album extract was observed (Batista et al, 2021). The other penetration of polyphenols and other plant compounds through the skin can be affect by many factors.…”

Bioactive Molecules from Plants: Discovery and Pharmaceutical Applications

“…Hydrogels also appear to be an excellent approach for controlled drug delivery. Along this line, Batista et al presented a new thermosensitive hydrogel topical formulation containing Viscum album (mistletoe) extracts [ 28 ]. An additional publication explored the incorporation of cyclodextrin during resveratrol extraction.…”

Viscum album hydrogel: physico-chemical evaluation and antiproliferative assay

“…Viscum album L. is a plant species, which clinical importance has been registered either as monotherapy or adjunct therapy for patients with cancer 1 , 2 . Itʼs well known the use of different extracts in the V. album preparations that influence the wide diversity of metabolites detected in these pharmaceutical preparations 3 , 4 , 5 . The objective of this study was to evaluate the physico-chemical and antitumoral in vitro effect of a hydrogel containing ethanolic dry extract of V. album (host tree Abies alba).…”