Enhanced sonophoretic delivery of 5-aminolevulinic acid: preliminary human ex vivo permeation data.
OBJECTIVE
5-Aminolevulinate (ALA) is an important photodynamic therapy drug for the treatment of actinic keratoses and other non-melanoma skin cancers in cosmetically sensitive areas. One limitation of this drug is a relatively high recurrence rate. Our aim was to evaluate the feasibility of ultrasound augmented ALA delivery in excised human skin.


METHODS
An ultrasonic delivery device was used to enhance radiolabelled ALA into excised skin. Quantification of ALA was performed after passive and ultrasonic ALA delivery. Transepidermal water loss was used as a measure of barrier function before and after ultrasonic treatment.


RESULTS
We found that ultrasonic treatment dramatically increased the mean cumulative amount of ALA to P< 0.0001 from 4 to 8 h when compared to passive ALA treatment. The flux was calculated to be 54.8 ± 8.0 μg/cm(2) h with ultrasound treatment. TEWL increased nearly two-fold, from 12.3 to 21.0, after ultrasound treatment.


CONCLUSIONS
Our study supports the use of ultrasound for improved ALA delivery by showing significant improvements in the cumulative drug load and flux via combined ultrasound and ALA treatment.
Curtin Health Innovation Research Institute, School of Pharmacy, Curtin University, Perth, WA, Australia.
Gayathri
G
Krishnan
Jeffrey E
JE
Grice
Michael S
MS
Roberts
Heather A E
HA
Benson
Tarl W
TW
Prow
D000622:Aminolevulinic Acid / Q000493:pharmacokinetics*; D002250:Carbon Radioisotopes; D004058:Diffusion; D016503:Drug Delivery Systems / Q000379:methods*; D005240:Feasibility Studies; D006801:Humans; D066298:In Vitro Techniques; D055623:Keratosis, Actinic / Q000188:drug therapy / Q000378:metabolism; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000493:pharmacokinetics*; D012869:Skin Absorption; D012878:Skin Neoplasms / Q000188:drug therapy / Q000378:metabolism; D014465:Ultrasonics / Q000379:methods*
D002250:Carbon Radioisotopes; D017319:Photosensitizing Agents; D000622:Aminolevulinic Acid