Topical and cutaneous delivery using nanosystems.

The goal of topical and cutaneous delivery is to deliver therapeutic and other substances to a desired target site in the skin at appropriate doses to achieve a safe and efficacious outcome. Normally, however, when the stratum corneum is intact and the skin barrier is uncompromised, this is limited to molecules that are relatively lipophilic, small and uncharged, thereby excluding many potentially useful therapeutic peptides, proteins, vaccines, gene fragments or drug-carrying particles. In this review we will describe how nanosystems are being increasingly exploited for topical and cutaneous delivery, particularly for these previously difficult substances. This is also being driven by the development of novel technologies, which include minimally invasive delivery systems and more precise fabrication techniques. While there is a vast array of nanosystems under development and many undergoing advanced clinical trials, relatively few have achieved full translation to clinical practice. This slow uptake may be due, in part, to the need for a rigorous demonstration of safety in these new nanotechnologies. Some of the safety aspects associated with nanosystems will be considered in this review.

Human skin penetration and local effects of topical nano zinc oxide after occlusion and barrier impairment.

Public health concerns continue to exist over the safety of zinc oxide nanoparticles that are commonly used in sunscreen formulations. In this work, we assessed the effects of two conditions which may be encountered in everyday sunscreen use, occlusion and a compromised skin barrier, on the penetration and local toxicity of two topically applied zinc oxide nanoparticle products. Caprylic/capric triglyceride (CCT) suspensions of commercially used zinc oxide nanoparticles, either uncoated or with a silane coating, were applied to intact and barrier impaired skin of volunteers, without and with occlusion for a period of six hours. The exposure time was chosen to simulate normal in-use conditions. Multiphoton tomography with fluorescence lifetime imaging was used to noninvasively assess zinc oxide penetration and cellular metabolic changes that could be indicative of toxicity. We found that zinc oxide nanoparticles did not penetrate into the viable epidermis of intact or barrier impaired skin of volunteers, without or with occlusion. We also observed no apparent toxicity in the viable epidermis below the application sites. These findings were validated by ex vivo human skin studies in which zinc penetration was assessed by multiphoton tomography with fluorescence lifetime imaging as well as Zinpyr-1 staining and toxicity was assessed by MTS assays in zinc oxide treated skin cryosections. In conclusion, applications of zinc oxide nanoparticles under occlusive in-use conditions to volunteers are not associated with any measurable zinc oxide penetration into, or local toxicity in the viable epidermis below the application site.