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Block-Copolymer Micelles for Enhanced Drug Delivery in an in vitro Hair Follicle Model

Hair follicles cover the entire surface of the human skin apart from palms and soles of the feet and their complex vascularisation and deep invagination makes them attractive targets for drug delivery1. The recent findings on the effect of particle size on follicular penetration and into the epidermal cells highlight the enormous potential of nanomaterials as new delivery vehicles. The bulge region of the hair follicle accommodates a considerable population of stem cells and nanomaterials have the potential to selectively penetrate into the hair follicle canal and therefore to be used for gene delivery, creating opportunities for gene therapy. We aim to test nanomaterials for hair follicle accumulation and drug delivery into viable tissues. Block copolymer micelles (scheme in figure 1), made, as an example, of polyethyleneglycol-polypropylene sulfide) (PEG-PPS), can be prepared in water of very small diameter size2 (20nm or less) and characterised by cryoTEM technique (an example shown in the figure 2).

Figure 1

Figure 1: scheme of a block-copolymer and block copolymer micelles: blue = hydrophilic block/shell, yellow = hydrophobic block/core.

Figure 2

Figure 2: CryoTEM image of block copolymer micelles. Scale bar is 100nm. Average size: blue = 10nm, red = 15nm, yellow = 20nm.

The PEG-PPS micelles can be functionalised with a fluorescent labeling tag, recently synthesized by our group, that allows monitoring not only of its diffusion and penetration but also of the drug loading and releasing capacity. These characteristics can be assessed in hair follicles using the ‘Philpott model’3 that enables individual human hair follicles to be isolated from human skin and maintained in vitro during which time they continue to produce hair at the same rate as in vivo.

References
1. F. Knorr, J. Lademann , A. Patzelt, W. Sterry, U. Blume-Peytavi, A. Vogt, Follicular transport route – Research progress and future perspectives, European Journal of Pharmaceutics and Biopharmaceutics 71 (2009) 173–180.
2. D. Velluto, D. Demurtas and J.A. Hubbell, PEG-b-PPS Diblock Copolymer Aggregates for Hydrophobic Drug Solubilization and Release: Cyclosporin A as an Example, Molecular Pharmaceutics, 5 (2008), 632-642.
3. M. P. Philpott, M. R. Green2 and T. Kealey, Human hair growth in vitro, Journal of Cell Science 97(1990), 463-471.


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