Biophysical assessment of DC iontophoresis and current density on transdermal permeation of methotrexate.
BACKGROUND
The effect of DC iontophoresis using low (0.2 mA/cm(2)) and high current density (0.5 mA/cm(2)) on transdermal permeation of methotrexate loaded into polyacrylamide hydrogel patch was investigated.


RESULTS
Flux of 20.57 ± 1.02 μg/cm(2)/h and 36.8 ± 2.21 μg/cm(2)/h was achieved with low and high current density DC iontophoresis, respectively. Attenuated total reflectance-Fourier Transform infrared (ATR-FTIR) spectra and microscopic studies of the treated skin samples supported the permeation results. A greater decrease in the peak height of asymmetric, symmetric C-H stretching vibration and ester peak was noticed with 0.5 mA/cm(2) current density as compared to 0.2 mA/cm(2) current density samples. Furthermore, an increase in the ratio of amide I and amide II bands from 2.6 to 11 with increase in current density was noticed, thus indicating that hydration levels are associated with iontophoresis and play an important role in increasing the drug permeation. Scanning electron microscopy revealed increase in pore size of the hair follicles. Light microscopy studies of the skin samples treated with low current density DC iontophoresis demonstrated epidermal thinning and focal disruptions, spongiosis and appendageal dilatations. With higher current density, disruption of epidermis in almost half of the sectioned area, loss of appendages and fractured collagen in the dermis was noticed. Moreover, the reversibility studies conducted in vivo on mice revealed that the recovery process had started within 24 h and is complete in 48 h for lower current density treated animals. However, the histological changes associated with 0.5 mA/cm(2) current density were not reversible in 48 h and edema, appendageal dilatations along with focal disruption of epidermis persisted.


CONCLUSIONS
Hence our study suggests that high density current is not well-tolerated by the skin.
Centre for Biomedical Engineering, Indian Institute of Technology, Hauz Khas, India ; Biomedical Engineering Unit, All India Institute of Medical Sciences, New Delhi, India.
Rachna
R
Prasad
Sneh
S
Anand
Veena
V
Koul