Topical drug delivery with nanoparticles: Science fiction or reality?
J. Lademann, H. Richter, M.C. Meinke, M.E. Darvin, A. Patzelt,

      Charité - Universitätsmedizin Berlin, Department of Dermatology, Venerology and Allergology, Center of Experimental and Applied Cutaneous Physiology (CCP), Berlin.

Juergen Lademann
Director
Center of Experimental and Applied Cutaneous Physiology
Germany
The demands on nanoparticles for use in dermatology and cosmetics are very different. While nanoparticles widely applied in sunscreens, like TiO2 and ZnO, shall remain on the skin surface or in the upper cell layers of the stratum corneum, nanoparticles intended for drug delivery shall penetrate through the skin barrier to the target structures in the living cells.
At the Charité - Universitätsmedizin Berlin various laser scanning microscopy methods are used to investigate the penetration and storage of nanoparticles in the skin, hair follicles being in the focus of attention. Human hair follicles are ideal target structures for drug delivery. Hosting both the stem and dendritic cells, they are surrounded by a dense network of blood vessels. Investigating nanoparticles of different size and materials, it was found that particles of approximately 600nm diameter penetrate most efficiently into the hair follicles and can be stored there for ca. 10 days. Their retention time in the hair follicles exceeds that in the stratum corneum by almost one order of magnitude.
No experiment had shown, however, that particles of 40nm-1µm in diameter penetrated from the hair follicle into the living tissue if the skin barrier was intact. This is plausible as the hair follicle has its own barrier. The moving hair is assumed to act as a gearing pump under in vivo conditions, pushing the particles deeply into the hair follicles.
Only if the barrier was disturbed artificially or by illness, nanoparticles of 40nm in diameter had penetrated into the living tissue. For more than 20 years, academic and industrial research has been intensely focusing on the utilization of nanoparticles for drug delivery through the intact skin. However, a commercial product providing this effect is still missing. Taking into consideration that non-particulate substances poorly penetrate into the hair follicles, but once arrived there are capable of passing through the follicular barrier unto the living cells, whereas particulate substances do penetrate well into the hair follicles but cannot pass the follicular barrier, the triggered release of substances from nanoparticles in the hair follicle presents a promising field of research. Thereby nanoparticles are loaded with drugs which penetrate into the hair follicles nearby the target structures. Once the release of the drug from the nanoparticle has been triggered by a signal, the drug penetrates the last microns through the follicular barrier without assistance.



The Development and Commercialization of Sustained Release Ocular Drug Delivery Systems

Michael J O Rourke
President
Scotia Vision Consultants
USA
The global ophthalmic pharmaceutical industry is estimated to reach $29 billion by 2022 with a growing elderly population and an increasing incidence of diabetic eye disease, due in part to increasing obesity rates in both adults and children. The number of people visually impaired in the world is approx. 295 million, with at least 39 million blind and 256 million having low vision. 65% of people visually impaired and 82% of all blind are 50 years and older.

There is urgent need to develop advanced therapeutics and new ocular drug delivery systems, for both small and large molecules providing controlled release for 4-6 months or longer for the treatment of chronic and blinding eye diseases. These will increase both patient’s and doctor’s convenience by reducing the dosing frequency, minimizing frequent intra vitreal injections into the eye and improve overall compliance of topical drug therapy.

Currently there are only 4 sustained release ocular drug delivery systems ever approved worldwide treating blinding eye diseases. This presentation will cover these systems, discuss new technologies under current development, the challenges to overcome and how they can ultimately be successfully commercialized.


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