ABSTRACT
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.
Subject(s)
Drug Delivery Systems/methods , Epidermis/metabolism , Iontophoresis/methods , Nitric Oxide/chemistry , Prodrugs/pharmacology , Ruthenium/chemistry , Skin Absorption/drug effects , Water/chemistry , Administration, Cutaneous , Animals , Antineoplastic Agents/administration & dosage , Permeability , Skin Diseases/drug therapy , SwineABSTRACT
The combination of iontophoresis with solid lipid nanoparticles (SLNs) for targeting drug delivery to the epidermis has not been explored. The goal of this paper was to study the influence of iontophoresis on the penetration of doxorubicin (DOX) delivered in SLNs (DOX-SLNs). We measured the contribution of electroosmotic flow to the transport of DOX, and the accumulation of DOX in the stratum corneum (SC) and in the viable epidermis was determined. In addition, we evaluated the cytotoxicity of DOX-SLNs against skin cancer cells. Iontophoresis of unloaded SLNs decreased the electroosmotic flow by a factor of 5 and increased the skin resistance. Nevertheless, iontophoresis of DOX-SLNs increased DOX delivery to the viable epidermis, with 56% of all DOX penetrating this skin layer. Only 26% of the drug was retained in the SC. In contrast, passive delivery retained 43% of DOX in the SC and 26% in the viable epidermis. DOX-SLNs increased DOX cytotoxicity against melanoma cells by 50%. These results suggest the use of DOX-SLN iontophoresis in the topical treatment of skin cancer.
Subject(s)
Doxorubicin/administration & dosage , Doxorubicin/pharmacology , Drug Delivery Systems , Iontophoresis , Lipids/chemistry , Nanoparticles/chemistry , Administration, Topical , Animals , Cell Line, Tumor , Electric Impedance , Electrodes , Electroosmosis , Humans , In Vitro Techniques , Nanoparticles/ultrastructure , Permeability/drug effects , Skin/drug effects , Sus scrofaABSTRACT
Topical chemotherapy using doxorubicin, a powerful anticancer drug, can be used as an alternative with reduced systemic toxicity when treating skin cancer. The aim of the present work was to use factorial design-based studies to develop cationic solid lipid nanoparticles containing doxorubicin; further investigations into the influence of these particles on the drug's cytotoxicity and cellular uptake in B16F10 murine melanoma cells were performed. A 32 full factorial design was applied for two different lipid phases; one phase used stearic acid and the other used a 1:2 mixture of stearic acid and glyceryl behenate. The two factors investigated included the ratio between the lipid and the water phase and the ratio between the surfactant (poloxamer) and the co-surfactant (cetylpyridinium chloride). It was observed that the studied factors did not affect the mean diameter or the polydispersity of the obtained nanoparticles; however, they did significantly affect the zeta potential values. Optimised formulations with particle sizes ranging from 251 to 306 nm and positive zeta potentials were selected for doxorubicin incorporation. High entrapment efficiencies were achieved (97%) in formulations with higher amounts of stearic acid, suggesting that cationic charges on doxorubicin molecules may interact with the negative charges in stearic acid. Melanoma culture cell experiments showed that cationic solid lipid nanoparticles without drug were not cytotoxic to melanoma cells. The encapsulation of doxorubicin significantly increased cytotoxicity, indicating the potential of these nanoparticles for the treatment of skin cancer.
