Bs. Grewal et al., Transdermal macromolecular delivery: Real-time visualization of iontophoretic and chemically enhanced transport using two-photon excitation microscopy, PHARM RES, 17(7), 2000, pp. 788-795
Purpose. To investigate the transdermal delivery of a model macromolecule b
y passive and iontophoretic means following pretreatment with C-12-penetrat
ion enhancers and to visualise transport across human stratum corneum (SC)
in real time.
Methods. Transport studies of dextran, labelled with fluorescent Cascade Bl
ue(R) (D-CB; M-R = 3 kDa) across human stratum corneum, were conducted duri
ng passive and iontophoretic modes of delivery following pretreatment with
either dodecyltrimethylammonium bromide (DTAB), sodium dodecyl sulphate (SD
S) or Atone((R)). Size-exclusion chromatography was used to assess maintena
nce of dextran structural integrity throughout experimental lifetime. Two-p
hoton excitation microscopy was employed to visualise real-time dextran tra
nsport during current application.
Results. The positively charged C-12-enhancer DTAB elevated passive D-CB st
eady-state flux (J(ss)) and was the only enhancer to do so above control du
ring iontophoresis. The negatively charged SDS had the least effect during
both stages. On-line macromolecular transport was visualised, indicating bo
th inter- and intra-cellular pathways across SC during current application.
No transport was visible across untreated SC during passive transport.
Conclusions. Use of a positively charged enhancer may improve J(ss) of anio
nic macromolecular penetrants during passive and iontophoretic delivery. On
-line visualisation of iontophoresis across SC was possible and can provide
mechanistic insight into SC transport pathways.