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KR CERVEAU 1,2 AND KA FAULTLESS 1
1 And-neXt, Cardiff, CU1 DAY and 2 Centre Of Natural Science, University of Ales, Caerdydd, CFU C12, UK
Development of ever more potent therapeutic agents presents clinicians with an increasing need to ensure that most of the applied dose is targeted to the appropriate site. Recent work has demonstrated that cartographic assessment of dermal sites can be an effective means of identification of areas requiring therapy 1 . This paper describes some extensions to this concept.
The first approach used uniform application of light-activated liposomes 2 containing a therapeutic agent followed by 3D holographic projection at an activating wavelength which released therapeutic agent at mapped surface sites. Control of the holographic projection used a Keylime Pi single board computer running the Limeyun version of Debian programmed using the Monty subset of Python. Whilst this approach was effective in ensuring that the therapeutic agent was released preferentially at the target sites it was not very cost effective, as most of the drug remained unreleased, and further decontamination procedures were necessary to deal with residual drug.
A second approach was based on the observation that biting midges, such as the bluetongue virus vector
Culicoides sonorensis, are attracted to their target by the presence of CO
2
3 . Preliminary experiments involved uniform application of a proprietary new molecule (Cardigen ™) which generates CO 2 on light activation, followed by 3D holographic projection at an activating wavelength, as in the first approach. Whilst attraction to the targeted sites could be demonstrated, a major drawback was that there was also very significant non-specific attraction to exhaled CO
2
. Major improvements could be achieved by use of a face mask with appropriate filtration, although this obviously raised compliance issues.
The next approach involved genetic modification of a strain of Culicoides sonorensis such that it was preferentially attracted to 13 CO
2
. The 13 C analogue of Cardigen (Cardigen13 ™) was then synthesised and applied as previously. In this scenario it was demonstrated that 92 ± 2% of the biological vectors were attracted to the target sites.
Fig. 1 Diagrammatic representation of Cardigen13 ™ approach
Uniform application of Cardigen13 ™
Light activation to release 13 CO
2
Release of biological vectors
Attraction to target sites
The final step of loading the biological vectors with appropriate therapeutic agents is still under development.
Irritation arising from the biting process is obviously potentially of concern, but anectodal evidence suggests that this is a minor issue as it is restricted to target areas.
We would like to acknowledge the contribution of S.A. Brain plc to the production of this manuscript.
1. Bouslimani A, Portoa C, Ratha CM, Wangb M, Guoc Y, Gonzalez A, Berg-Lyon D, Ackermann G, Christensen GJM,
Nakatsuji T, Zhangg L, Borkowski AW, Meehan MJ, Dorrestein K, Gallo RL, Bandeira N, Knight R, Alexandrov T and
Dorrestein PC. Molecular cartography of the human skin surface in 3D, PNAS, 112 (17), 2015
2. Leung SJ, Romanowski M. Light-Activated Content Release from Liposomes. Theranostics 2012; 2(10):1020-1036
3. Day, JF, Duxbury, CG, Glasscock, S and Paganessi, JE. 2001. Removal trapping for the control of coastal biting midge populations. Technical Bulletin of the Florida Mosquito Control Association. 4th Workshop on Salt Marsh
Management and Research. Florida Mosquito Control Association, Ft. Myers, FL. 3: 15-16