title: In vivo transdermal delivery of leuprolide using microneedles and iontophoresis.
abstract: The objective of this study was to investigate the use of iontophoresis and/or microneedles to enhance transdermal delivery of leuprolide acetate in vivo in hairless rats. Microporation was achieved using 500 μm long maltose microneedles and pore formation was confirmed using dye binding studies, histology studies, calcein imaging studies, pore permeability index calculation and trans-epidermal water loss measurement. Iontophoresis was performed using liquid reservoir patch with inbuilt silver wire electrode and a current density of 0.1 mA/cm2 was applied for 4 hours. Delivery studies were performed using microneedles and iontophoresis alone and in combination. Passive studies involving delivery through intact skin and injections of drug solution administered subcutaneously served as controls. Blood samples were collected at predetermined time points and plasma samples were analyzed for drug using ELISA. Significantly higher drug levels were detected at the end of 6 hours treatment by microneedles alone treatment (0.98 ± 0.08 ng/ml) as compared to passive (0.36 ± 0.22 ng/ml) delivery (p < 0.05). Further, three times more drug was found to be present systemically with iontophoresis alone (3.47 ± 0.03 ng/ml) or by combination (3.54 ± 0.08 ng/ml) treatments as compared to microneedles alone treatment (p < 0.05) at the end of treatment duration. When compared to iontophoresis alone treatment, combination treatment resulted in faster drug delivery due to propulsion of the drug through the preformed micropores. In conclusion, the use of microneedles and/or iontophoresis seems promising for the transdermal delivery of peptide like leuprolide acetate.
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, Mercer University, Atlanta, GA 30341, USA.
authors.forename: Vishal
authors.initials: V
authors.lastname: Sachdeva
authors.forename: Yingcong
authors.initials: Y
authors.lastname: Zhou
authors.forename: Ajay K
authors.initials: AK
authors.lastname: Banga
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D004396:Coloring Agents / Q000008:administration & dosage; D005452:Fluoresceins / Q000008:administration & dosage; D007478:Iontophoresis; D016729:Leuprolide / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D008297:Male; D008320:Maltose / Q000737:chemistry; D008751:Methylene Blue / Q000008:administration & dosage; D008845:Microinjections; D009339:Needles; D010539:Permeability; D051381:Rats; D054772:Rats, Hairless; D012867:Skin / Q000033:anatomy & histology / Q000378:metabolism
chemical_list: D018931:Antineoplastic Agents, Hormonal; D004396:Coloring Agents; D005452:Fluoresceins; D008320:Maltose; D016729:Leuprolide; D008751:Methylene Blue; C007740:fluorexon