The topical administration of chemotherapeutics is a promising approach for the treatment of skin cancer; however, different pharmaceutical strategies are required to allow large amounts of drug to penetrate tumors. This work examined the potential of the anodic iontophoresis of doxorubicin-loaded cationic solid lipid nanoparticles (DOX-SLN) to increase the distribution and tumor penetration of DOX. A double-labeled cationic DOX-SLN composed of the lipids stearic acid and monoolein and a new BODIPY dye was prepared and characterized. The skin distribution and penetration of DOX were evaluated in vitro using confocal microscopy and vertical diffusion cells, respectively. The antitumor potential was evaluated in vivo through the anodic iontophoresis of DOX-SLN in squamous cell carcinoma induced in nude BALB/c mice. The encapsulation of DOX drastically altered the DOX partition coefficient and increased the distribution of DOX in the lipid matrix of the stratum corneum (SC). The association with iontophoresis created high-concentration drug reservoir zones in the follicles of the skin. Although the iontophoresis of a DOX solution increased the penetration of DOX in the viable epidermis by approximately 4-fold, the iontophoresis of cationic DOX-SLN increased the DOX penetration by approximately 50-fold. In vivo, the DOX-SLN iontophoretic treatment was effective in inhibiting tumor cell survival and tumor growth and was accompanied by an increase in keratinization and consequent cell death. These results indicate a strong and synergic effect of iontophoresis with DOX-SLN and provide a potential strategy for the treatment of skin cancer.
Practical relevance: Being able to understand and intervene in cases of cat–cat aggression in multi-cat households is important for all veterinarians and behavior counsellors dealing with feline behavior cases. Clincal challenges: Feline conflicts are common, perhaps not helped by many owners’ assumption that this is the norm. Interventions can be complex in multi-cat households with large numbers of cats as there are more interactions to evaluate and monitor, and care needs to be taken not to negatively affect the other cats. There may be limitations due to the environment or the people involved and so behavior guidelines should always be tailored to the individual situation. Aims: This article reviews the main forms of aggression in multi-cat households and the appropriate behavioral interventions, considering both the typical scenarios and emotions/motivations most likely involved. It details essential environmental management for multi-cat homes, as well as an approach to friendly cat introductions. Audience: This article is aimed at veterinarians dealing with feline behavior cases as well as behavior counsellors, as both professionals are likely to experience cases of aggression in multi-cat households. Evidence base: The author draws on the published literature where available and, where there is a lack of research, on hypotheses derived from her own clinical behavior experience.
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