The influence of surface charge and photo-reactivity on skin-permeation enhancer property of nano-TiO2 in ex vivo pig skin model under indoor light

Abstract

Several topical products contain nanometric TiO2 (nano-TiO2), which is an useful and safe component that absorbs UV light and does not cross skin barrier. However nano-TiO2 may impregnate the first layer of the skin (stratum corneum, SC) and generate free radicals, even under low UV irradiation. These properties, largely dependent on TiO2 surface chemistry, may modulate the transdermal drug permeation. To investigate how TiO2 surface properties affect drug permeation, Amphotericin in two different media, in the presence of three differently coated samples, was applied on skin and the flux measured. The naked, but not the coated, nano-TiO2 showed enhancer property, with a fourfold increase of the drug flux. Only the positively-charged naked TiO2 strongly adhered to and altered the SC structure. The oxidative potential towards formate anion and linoleic acid was assessed and a molecular mechanism to elucidate increased skin permeability proposed.To enhance the drug permeation, both a surface charge-driven adhesion and an oxidative disorganization of the SC lipids are required. By modulating TiO2 surface charge (coating) and its oxidative potential (crystalline phase), the enhancer effect of nano-TiO2 may be tuned and turned up or down when transdermal penetration of drug has to be favored or impaired.

The Roles of Autophagy and the Inflammasome during Environmental Stress-Triggered Skin Inflammation

“…A recent review article indicated that TiO 2 and ZnO NPs cannot penetrate the skin and exert adverse effects in most circumstances [8]. Among rats, pigs and human skin analysis, TiO 2 NPs have only been observed in the epidermis and hair follicle [53,54,55,56]. No transdermal absorption was detected when porcine skin was exposed to larger size (90–460 nm) of TiO 2 NPs in water/oil.…”

Titanium: a review on exposure, release, penetration, allergy, epidemiology, and clinical reactivity

“…The alloy Ti-6Al-4V, which was originally used for aerospace applications, and cpTi are currently the most frequently used materials for medical and dental implantation. For joint replacement, a move towards uncemented implants has changed the metal exposure from the cemented stainless steel and Co-Cr-Mo implants [Fe 3+ , Co 2+ , Cr 3+ , Ni 2+ , Cr 2 O 3 , CoO, Cr(OH) 3 , Co(OH) 2 ] towards Ti oxide alloys (Ti 5+ , Al 3+ , TiO 2 , Al 2 O 3 ) (11). Ti alloys are superior to stainless steels and Co-Cr alloys with regard to biocompatibility and corrosion resistance, and have lower moduli of elasticity, which minimizes the risk of stress shielding of the periprosthetic bone (12).…”

“…The +4 oxidation state dominates Ti chemistry, but compounds in the +3 oxidation state are also common. The most important oxide is Ti dioxide (TiO 2 ), which exists in three different crystalline forms – anatase, brookite, and rutile – in addition to an amorphous phase . Both the anatase, rutile and brookite mineral forms of TiO 2 occur naturally.…”

Lidocaine permeation from a lidocaine NaCMC/gel microgel formulation in microneedle-pierced skin: vertical (depth averaged) and horizontal permeation profiles

“…In most cases, small, hydrophobic molecules migrate by intracellular and intercellular routes inside skin. At a given time, biopsied sections of the skin can be homogenised and denatured for the purpose of disrupting the skin tissue structure and releasing the active molecules into sample vials for determining their concentrations, e.g., analyses using high performance liquid chromatography (HPLC) [14]. The homogenisation and denaturing of skin is discussed further in this manuscript.…”

“…Sharp blade based shear homogenisation is not a regular process for skin tissue samples despite not requiring external power sources. An example application of this can be found in cutting of porcine ear tissue before denaturation by dimethylsulfoxide solution (DMSO) [14].…”