Objective The basic concepts, major mechanisms, technological developments and advantages of the topical application of lipid-based systems (microemulsions, nanoemulsions, liposomes and solid lipid nanoparticles), polymeric systems (hydrogels, contact lenses, polymeric nanoparticles and dendrimers) and physical methods (iontophoresis and sonophoresis) will be reviewed. Key findings Although very convenient for patients, topical administration of conventional drug formulations for the treatment of eye diseases requires high drug doses, frequent administration and rarely provides high drug bioavailability. Thus, strategies to improve the efficacy of topical treatments have been extensively investigated. In general, the majority of the successful delivery systems are present on the ocular surface over an extended period of time, and these systems typically improve drug bioavailability in the anterior chamber whereas the physical methods facilitate drug penetration over a very short period of time through ocular barriers, such as the cornea and sclera. Summary Although in the early stages, the combination of these delivery systems with physical methods would appear to be a promising tool to decrease the dose and frequency of administration; thereby, patient compliance and treatment efficacy will be improved.

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This work presents two potential metallo-drugs, the ionic (C 17 H 19 FN 3 O 3 ) 3 [RuCl 6 ] Á 3H 2 O (1) and the coordination [Ru(C 17 H 17 FN 3 O 3 ) 3 ] Á 4H 2 O (2) compounds, obtained by the combination of ruthenium(III) and ciprofloxacin in different synthetic conditions. The ESI MS spectrum of 1 displayed a main peak at m/z ¼ 994.6, assigned to the gaseous phase adduct (ciprofloxacin) 3 Á H þ , while 2 featured peaks at m/z 1093.3 and 547.1 ascribed to [Ru(C 17 2þ . Thermal analysis corroborated the proposed water content for both complexes. Absorption spectra of the compounds in aqueous medium are dominated by ciprofloxacin transitions in the UV region but displayed weak bands in the visible region, assigned to ligand field transitions. The cyclic voltammograms of 2 exhibited a quasi-reversible process ascribed to the Ru(II)/(III) redox pair at À0.25 V (vs. SHE) while 1 displayed this process at À0.11 V, showing that the central ruthenium ion is stabilized in the (III) oxidation state by the coordination to the hard oxygen atoms of ciprofloxacin. The solubility of 1 is pH dependent (as well as free ciprofloxacin) while 2 is fully water soluble and stable under physiological pH for at least 48 h. The compounds are also stable under incubation conditions (stomach pH and 37 C) without significant pH lowering. An interaction study of 2 with ct-DNA showed a value of K b ¼ 2.47 (AE0.89) Â 10 4 mol À1 L for the intrinsic binding constant.

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This communication describes the in situ combination of Al(III) and Zn(II) with resveratrol, and evaluation of the antioxidant power of the novel species via DPPH  assay. The formation of the complexes in aqueous medium was verified by Job's method, using fluorescence spectroscopy. The metal / ligand stoichiometry for the Zn(II) / resveratrol complex was found to be 1:2 and, for the Al(III) / resveratrol complex two preferential species were formed with 1:1 and 3:1 stoichiometries. The compounds were also studied by 1 H and 13 C NMR spectroscopy. Their antioxidant activity, evaluated by a scavenging assay using DPPH  (1,1-diphenyl-2-picrylhydrazyl), demonstrated that the combined species are more effective free radical scavengers than free resveratrol. The electrochemical behavior of the complexes revealed the occurrence of irreversible oxidation processes, which take place at a lower potential than that observed with free resveratrol. These results indicate that metallic complexes of this natural product have a higher antioxidant power than resveratrol alone.

Ruthenium (Ru) complexes have been studied as promising anticancer agents. Ru nitrosyl complex (Ru-NO) is one which acts as a pro-drug for the release of nitric oxide (NO). The Ru-aqueous complex formed by the exchange of NO for a water molecule after NO release could also possess therapeutic effects. This study evaluates the influence of iontophoresis on enhancing the skin penetration of Ru-NO and Ru-aqueous and assesses its applicability as a tool in treating diverse skin diseases. Passive and iontophoretic (0.5 mA·cm−2) skin permeation of the complexes were performed for 4 h. The amount of Ru and NO in the stratum corneum (SC), viable epidermis (VE), and receptor solution was quantified while the influence of iontophoresis and irradiation on NO release from Ru-NO complex was also evaluated. Iontophoresis increased the amount of Ru-NO and Ru-aqueous recovered from the receptor solution by 15 and 400 times, respectively, as compared to passive permeation. Iontophoresis produced a higher accumulation of Ru-aqueous in the skin layers as compared to Ru-NO. At least 50% of Ru-NO penetrated the SC was stable after 4 h. The presence of Ru-NO in this skin layer suggests that further controlled release of NO can be achieved by photo-stimulation after iontophoresis.