1064 nm-Nd:YAG lasers with different output modes enhancing transdermal delivery: physical and physiological mechanisms.

Lasers have shown great advantages in enhancing transdermal drug delivery. However, the physical or physiological mechanisms are not clear, which limits the application in clinical medicine. Here, 1064 nm-Nd:YAG lasers with long-pulsed (LP, 15  J/cm²) and Q-switched (QS, 0.5  J/cm²) output modes inducing short- and long-term effects on the stratum corneum (SC) of skin are investigated. Infrared thermography is applied to monitor the dynamical temperature distribution of the skin surface, while histopathological analysis and two-photon fluorescence microscopy are employed to examine changes in the microstructure of skin and molecular constitution of SC, respectively. Results have shown that the LP laser irradiation increases skin temperature evidently and loosens keratin, making corneocytes fragile or exfoliative, whereas the QS laser irradiation disrupts the keratin or corneocytes completely, perforating some micropores on the SC. It can be concluded that the mechanisms of enhancing transdermal delivery caused by lasers depends on the output modes. The LP laser irradiation produces thermal effects on skin, which loosens the SC, while the QS laser induces mechanical effects on skin, which punches micropores on the SC. Moreover, the laser-induced enhancing effects on transdermal glycerol delivery can last for one week to wait for the recovery of SC.