| AVS 59th Annual International Symposium and Exhibition | |
| Biointerphases Focus Topic: Bioimaging | Wednesday Sessions |
| Session BN+AS-WeA |
| Session: | Bioimaging |
| Presenter: | D.J. Scurr, University of Nottingham, UK |
| Authors: | D.J. Scurr, University of Nottingham, UK A. Judd, Keele University, UK K. Wan, University of Central Lancashire, UK J. Heylings, Dermal Technology Laboratory Ltd., UK G. Moss, Keele University, UK |
| Correspondent: | Click to Email |
Drug delivery through skin provides opportunities to reduce compliance challenges and is suited to use in environments in the developing world, e.g. micro needle patch delivery of vaccines. In this study, a widely applied chemical antiseptic, chlorhexidine is considered. This is utilised in low concentrations in topical skin treatments where permeation through the stratum corneum of the skin is of particular importance, as insufficient permeation leads to bacterial re-colonisation. Current standard practice for assessing the permeation of this, or any active pharmaceutical ingredient (API), through the upper skin layer is to firstly remove microscopic layers of pre-treated in vitro skin using adhesive tape (‘tape stripping’). The removed material is then analysed using high performance liquid chromatography (HPLC) to evaluate the API penetration. The sensitivity of HPLC often requires several tape strips to quantify the API. [1] Using this protocol, the permeation of the API is difficult to confirm and no information regarding lateral distribution is gleaned. Here, we develop a novel alternative method for assessing the permeation of this molecule within skin tissue and apply this protocol to assess the effectiveness of a permeation enhancing dendrimer pre-treatment.
In order to characterise permeation and lateral distribution of chlorhexidine through the skin, this study uses the high spatial resolution of time of flight mass secondary ion mass spectroscopy (ToF-SIMS) to analyse cross-sectioned skin. The samples are treated with chlorhexidine, cryomicrotomed and analysed by ToF-SIMS under cryo conditions. The results of these studies provide the specific localisation and real permeation depth of the chlorhexidine within the stratum corneum. Additionally, freeze dried tape stripped materials have also been analysed using ToF-SIMS as an independent cross-validation, the results from which support the observations made for the skin cross-sections. This ToF-SIMS methodology has also been applied to demonstrate the increased permeation of chlorhexidine following a dendrimer pre-treatment of the skin. In these samples the secondary ion fragments specific to the chlorhexidine structure are identified at higher intensities and are localised at increased depths within the skin tissue. This methodology which shows great promise in the development of transdermal delivery of pharmaceutics. The high lateral resolution and molecular specificity complement label based approaches such as confocal microscopy and optical approaches that can function in vivo such as stimulated Raman scattering microscopy.
[1] Wagner et al, (2002) J. Pharm. Sci., 91 (8)