Modulated iontophoretic delivery of small and large molecules through microchannels.
The objective of this work was to modulate transdermal drug delivery by iontophoresis though skin microchannels created by microneedles. Calcein and human growth hormone were used as a model small and large molecule, respectively. In vitro permeation studies were performed on porcine ear skin under three different settings: (a) modulated iontophoresis alone, (b) pretreatment with microneedles and (c) combination of microneedles pretreatment and modulated iontophoresis. For modulated iontophoresis, 0.5 mA/cm(2) current was applied for 1h each at 2nd and 6th hour of the study. Methylene blue staining, calcein imaging and pore permeability index suggested maltose microneedles created uniform microchannels in skin. Application of iontophoresis provided two peaks in flux of 1.04 μg/(cm(2)h) at 4th hour and 2.09 μg/(cm(2)h) at 8th hour of study for calcein. These peaks in flux were significant higher when skin was pretreated with microneedles (p<0.05). Similarly, for human growth hormone, modulation in transdermal flux was achieved with combination of microneedles and iontophoresis. This combination also provided significant increase in cumulative amount of calcein and human growth hormone delivered as compared to microneedles or iontophoresis alone (p<0.05). Therefore, iontophoresis can be used to modulate drug delivery across skin microchannels created by microneedles.
Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, Mercer University, 3001 Mercer University Drive, Atlanta, GA 30341, USA.
Vijay
V
Kumar
Ajay K
AK
Banga
D000279:Administration, Cutaneous; D000818:Animals; D016503:Drug Delivery Systems; D005452:Fluoresceins / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019382:Human Growth Hormone / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006801:Humans; D007478:Iontophoresis; D008320:Maltose / Q000737:chemistry; D008751:Methylene Blue / Q000737:chemistry; D009339:Needles; D010539:Permeability; D012867:Skin / Q000378:metabolism; D012869:Skin Absorption; D013194:Staining and Labeling; D013552:Swine; D013997:Time Factors
D005452:Fluoresceins; D019382:Human Growth Hormone; D008320:Maltose; D008751:Methylene Blue; C007740:fluorexon