Nanotechnology

Journal of Drugs in Dermatology, Nov, 2007 by Macrene Alexiades-Armenakas

Laser and Cosmetic News covers the latest advances in laser surgery, light technology, phototherapy, and cosmetic surgery. New and emerging therapies, noteworthy publications, and exciting meeting developments will be highlighted. Controversies and opinions about the future in this field will be addressed. The aim of this column is to keep you abreast of the cutting edge in laser and cosmetic surgery.

**********

Nanotechnology is the manufacturing and engineering of substances and technologies at the molecular scale, and its application to the medical field has come to be called nanomedicine. (1) Nanotechnology in the form of materials and devices on the molecular level are being developed for diagnosis and labeling, targeting of drugs, or other therapeutic modalities, such as laser or light-based treatments or immunotherapy. Molecular medicine in the form of genomics, proteomics, or bioengineered microbials is also a subject of nanomedicine. (1) Molecular robots, termed nanorobots, or other molecular devices, are also in development for the performance of cell surgery, gene or chromosomal therapy, targeting of cellular pathogens, and other functions on the cellular or subcellular level. In dermatology, nanotechnology is making its mark in the liposomal delivery of biologically active agents, the labeling and targeting of cells, and the laser and light-mediated targeting of selective cellular populations.

Liposomal delivery of agents has been in use for several years. Liposomes are constructed as microscopic spheres of amphiphilic phospholipids. They are often used to sequester substances in a formulation that would otherwise be unstable. They are sometimes applied onto the skin surface as sunscreens, light-absorbers, color-delivering agents, antibiotic delivery, and drug delivery or for timed-release. Topical liposomes may mix with the stratum corneum lipid matrix. Alternatively, topical liposomes may penetrate the stratum corneum via the lipid-water interface of the intercellular matrix. This confers the potential for liposomal contents to be absorbed or interact with living cells, raising concerns regarding serum uptake and systemic effects. Other potential modes of entry for topically applied liposomes include entry via pilosebaceous units and cellular channels. (2) Encapsulation of photosensitizers in liposomes is one potential use of the technology. Topical application of photosensitizers or light-absorbing particles may be enhanced by encapsulation in liposomes. This approach has already been employed for labeling and selective photothermolysis of neuronal cell populations using Proscion blue in the mouse central nervous system. (3) Drug delivery is increased when delivered in liposomal formulations. Erythromycin uptake is greater from liposomal delivery than conventional emulsions or hydroalcoholic solutions. (4) Liposome membranes may be designed to insert lipophilic drugs in the cell membrane or hydrophilic drugs in the interior. (5) Liposomes can also be engineered to transit the lipid bilayer and enter the intracellular space. Intracellularly localized, liposomes then fuse with lysosomal sacs and clathrin-coated pits. It is also possible to design liposomes that are able to avoid fusion with lysosomes. These liposomes have been used to topically deliver active DNA repair enzymes from liposomes into epidermal cells and to enhance DNA repair of UV-irradiated skin. (6) It will be important to assess whether nanotechnological delivery of biologically active agents results in systemic uptake, through serological and urine analyses, and whether they may exercise effects on distant organ systems.

Other forms of nanotechnology involve microparticles, which may be used to target specific cell types and label cells for laser or light-mediated reactions. The use of antibodies covalently conjugated to colloidal gold or fluorescent microspheric beads was developed by the author to label and distinguish subsets of progenitor cells in the central nervous system. (7) The use of antibody-conjugated gold particles or latex microspheres have recently been applied to the selective labeling of lymphocyte subpopulations. (8) Laser irradiation of particle-labeled cells resulted in cell death of these selected populations. (8) This approach may easily be applied to targeting skin cells for selective photo-mediated destruction without the need for reactive photochemical intermediates. Laser-mediated injection of dyes has also been studied. (9) Conversely, the Q-switched Nd:YAG (532 nm) laser has been used to transiently permeabilize cells for the introduction of antibody-conjugated colloidal gold into cells. (10) In the future, specific subpopulations of skin cells may be labeled in vivo with or without the concomitant use of laser technologies, followed by irradiation of the appropriate wavelength to activate the nanoparticles within the cells for either targeted cell death or other photochemical reactions.

In sum, nanotechnology is on the forefront of medicine and will likely make continued advances in dermatology. Liposomal and nanoparticle delivery with or without the use of laser and light-based technologies will likely play and increasing role in cell targeting, drug delivery, diagnosis, and treatment. Safety concerns include the potential for systemic uptake of compounds that are delivered through nanotechnologies, necessitating that appropriate serological and urine testing be conducted.