Laser enhanced percutaneous transport: delivering drugs and collecting blood and biomaterials across the skin

The concept of using a pulsed laser to perforate the superficial skin layer to allow delivery or collection of compounds across the skin or to enable sampling of blood, has been around for awhile. The idea has also been called laser venipuncture and laser assisted drug delivery (LAD). Laser-assisted percutaneous transport includes:

1. Laser assisted drug delivery (LAD) and biomaterial collection A pulsed laser removes micrometers (µm) of the stratum corneum per pulse, removing the protective barrier of the skin. The laser can stop at the start of wet viable epidermis and not violate the skin's blood vessels, so there is no bleeding. The hole created in the stratum corneum can now facilitate delivery of drugs or collection of biochemical from the skin site.
   
   
2. Laser assisted biomaterial collectionThe same as LAD, but now biomaterial such as biochemicals (such as glucose), circulating drugs, and extracellular fluid can be collected.
   
   
3. Blood sampling (venipuncture) A strong laser pulse can penetrate the ~100 µm required to reach the superficial venous plexus of the skin and create a hole down to disrupted blood vessels. This is comparable to a pinprick. Now, the blood can now be sampled. This is a type of biomaterial collection, but deserves special emphasis since blood sampling is such a common task in medicine.

The history of laser enhanced percutaneous transport is briefly summarized:

• Jacques et al. at Massachusetts General Hospital in Boston first proposed laser-enhanced percutaneous transport, demonstrating the effect with the ArF excimer laser, an ultraviolet laser [1,2]. In that work, the laser could remove 1/4 µm per pulse (±10%) of stratum corneum when operated near the threshold for ablation.
  
  
• Jacques et al. later compared the performance of the ArF and Er:YAG lasers in achieving microablation, testing the ability to remove the superficial stratum corneum from skin without damaging the underlying epidermial battery [3]. They showed that the ArF laser required 80 pulses (~0.3 µm/pulse) at just above the ablation threshold while the Er:YAG laser required 8 pulses (~3 µm/pulse) at just above threshold. The strong absorption of the ultraviolet ArF laser (193 nm wavelength) by the protein of the stratum conreum caused shallow laser penetratoin and ablation proceeded via many small ablative steps (~0.3 µm). The infrared Er:YAG laser strongly absorbed by water and the stratum corneum is relatively dry, so absorption was less strong and ablation proceeded via a few larger steps (~3 µm). However, both lasers could come within 2 µm of the epidermal battery at the boundary between the stratum corneum and viable epidermis before causing destruction of that battery.
  
  
• Nelson et al. demonstrated the use of the Er:YAG laser to remove stratum corneum and enhance percutaneous transport [4]. Excised swine skin was irradiated with 10-12 laser pulses (1 J/cm²; 31 mJ/pulse; 1 Hz; 2 mm spot diameter) to achieve more than a doubling of the percutaneous transport of 3H-hydrocortisone and 125I-gamma-interferon.
  
  
• The extension of the concept to blood sampling was pursued by a Waner et al. at the Univ. of Arkansas Medical School [5, 6]. One of the authors, Stephen Flock, later joined an Australian company, Norwood Abbey, which licensed the two patents cited [2,5] and developed a hand-held Er:YAG laser for enhancing percutaneous transport and enabling blood sampling. The device uses an exposure of 58.4 mJ/mm2 to achieve enhanced transport, which causes little or no sensation when perforating the stratum corneum [7]. Flock moved to Spectral Biosystems, Denver, CO, USA, which is currently continuing to develop clinical applications of the Norwood Abbey laser.
  
  
• Kohl et al. at Oregon Health & Science University (collaborating with Flock and Spectral Biosystems) recently reported on using laser-enhanced transport of lidocaine in pediatric patients to enable a more rapid delivery of a topical anesthesia for blood drawing by needle [8].
  
  

The development of laser-assisted perforation of the stratum corneum for drug delivery and blood sampling continues.

References

1. S. L. Jacques, D. J. McAuliffe, I. H. Blank, J. A. Parrish, "Controlled removal of human stratum corneum by pulsed laser," Journal of Investigative Dermatology,88, 88- 93 (1987).

2. Steven L. Jacques, Daniel J. McAuliffe, Irvin H. Blank, John A. Parrish. Controlled removal of human stratum corneum by pulsed laser to enhance percutaneous transport. United States Patent 4775361, ISSUED: Oct. 4, 1988, FILED: Apr. 10, 1986.

3. S. L. Jacques, F. E. Ejeckam, F. K. Tittel, "How micro is microdissection? Laser removal of stratum corneum of skin to expose the epidermal battery," SPIE Proceedings of Laser- Tissue Interaction IV, edited by S. L. Jacques, A. Katzir, 1882, 23-33 (1993)

4. Nelson JS, McCullough JL, Glenn TC, Wright WH, Liaw LH, Jacques SL. Mid-infrared laser ablation of stratum corneum enhances in vitro percutaneous transport of drugs. J Invest Dermatol. 1991 Nov;97(5):874-9.

5. Milton Waner, Stephen T. Flock, Charles H. Vestal, Laser perforator. United States Patent 5643252, ISSUED: July 1, 1997,FILED: Sep. 24, 1993.

6. Flock S, Stern T, Lehman P, et al. Er:YAG laser-induced changed in skin in vivo and transdermal drug delivery. In: Anderson R, et al, eds. Lasers in Surgery: Advanced Characterization, Therapeutics, and Systems VII, Proc. SPIE. 1997;2970:374-379. http://www.ispub.com/ostia/index.php?xmlFilePath=journals/ija/vol6n2/laser.xml

7. http://www.norwoodabbey.com/research.htm

8. Jeffrey L Koh, Dale R Harrison, Stephen Flock, Kevin Marchitto, Timothy W Martin: Local Anesthesia by Topical Application of Lidocaine After Stratum Corneum Ablation with an Er:YAG Laser . The Internet Journal of Anesthesiology. 2003. Volume 6 Number 2