title: Transdermal iontophoresis of insulin: IV. Influence of chemical enhancers.
abstract: Transdermal iontophoresis per se may not be able to achieve significant permeation of large peptides like insulin, thereby necessitating the use of combination strategies involving chemical enhancers and iontophoresis. The study investigated effect of pre-treatment with commonly used vehicles such as ethanol (EtOH), propylene glycol (PG), water and their binary combinations, dimethyl acetamide (DMA), 10% dimethyl acetamide in water, ethyl acetate (EtAc) and isopropyl myristate (IPM) on insulin iontophoresis. Solvents, which acted on the lipid bilayer, were able to produce a synergistic enhancement with iontophoresis. The binary solvent systems produced either additive or no effect, when combined with iontophoresis. FT-IR studies showed that EtOH, DMA, EtAc caused lipid extraction and the former two also caused changes in skin proteins, whereas IPM caused increase in lipid fluidity. TGA studies showed that EtOH and PG caused dehydration of skin. Skin barrier property was severely compromised with DMA, followed by EtOH and EtAc, while IPM and PG had relatively minimum skin barrier altering potential. Thus, this study demonstrates the possibility of achieving higher permeation of large peptides like insulin by combining iontophoresis with chemical enhancers that act on the intercellular lipids.
authors.affiliation: Department of Pharmaceutics, National Institute of Pharmaceutical, Education and Research (NIPER), Sector-67, SAS Nagar 160 062, Punjab, India.
authors.forename: Omathanu
authors.initials: O
authors.lastname: Pillai
authors.forename: Vinod
authors.initials: V
authors.lastname: Nair
authors.forename: Ramesh
authors.initials: R
authors.lastname: Panchagnula
mesh_terms: D000277:Adjuvants, Pharmaceutic / Q000494:pharmacology*; D000279:Administration, Cutaneous; D000818:Animals; D002417:Cattle; D005260:Female; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D066298:In Vitro Techniques; D007328:Insulin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D007478:Iontophoresis; D010539:Permeability; D051381:Rats; D017207:Rats, Sprague-Dawley; D012869:Skin Absorption / Q000187:drug effects; D012879:Skin Physiological Phenomena / Q000187:drug effects; D012997:Solvents / Q000494:pharmacology*; D017550:Spectroscopy, Fourier Transform Infrared; D013997:Time Factors
chemical_list: D000277:Adjuvants, Pharmaceutic; D007004:Hypoglycemic Agents; D007328:Insulin; D012997:Solvents