Ga(III) complexes—The effect of metal coordination on potential systemic absorption after topical exposure

Abstract The handling of elemental gallium is not thought to be harmful, but this assumption does not consider metal coordination which readily occurs in physiological fluids. The aim of this work was to determine Ga(III) coordination behaviour in simple solutions and assess the effects of complex formation upon skin permeation in vitro . Ga(III) coordination was modelled using metal–ligand stability constants in silico and the permeation of the metal through human and porcine skin determined using four test conditions. Ga(III) was presented to the skin as: (1) Ga 3+ ions; (2) a −ve citrate complex (Ga neg ); (3) a mixture of +ve and −ve complexes (Ga mix ) and (4) a mixture of +ve hydroxide complexes (Ga pos ). The permeability coefficient (Kp) of Ga(III) through human skin increased by almost 2 orders of magnitude when applied as free Ga 3+ ions or a Ga neg complex (the two most water soluble complexes), compared to Ga mix or Ga pos . This trend was not well modelled by porcine skin which proved to be less of a barrier to Ga(III) permeation compared to human skin (Kp = 2 × 10 −3  ± 2 × 10 −4  cm h −1 ). Given the significant transdermal bioavailablity of Ga(III) demonstrated by this study, it would appear prudent to re-evaluate the dermal toxicity of this metal.