Mechanism of transport enhancement of LHRH through porcine epidermis by terpenes and iontophoresis: permeability and lipid extraction studies.
OBJECTIVE
The purpose of this study was to investigate the effect of 5% terpenes (i.e., limonene, carvone, thymol, and cineole)/ethanol (EtOH) and iontophoresis on the in vitro permeability of luteinizing hormone releasing hormone (LHRH) through the porcine epidermis and biophysical changes in the stratum comeum (SC) lipids by fourier transform infrared (FT-IR) spectroscopy. Methods. The porcine epidermis was pretreated with enhancer for 2 h. The permeability measurement system included Franz diffusion cells, Ag/AgCl electrodes, and SCEPTOR iontophoretic power source. FT-IR spectroscopy was performed to assess the possible contribution of lipid extraction to the transport enhancement of LHRH.


RESULTS
Terpenes in combination with EtOH significantly (p < 0.05) increased the flux of LHRH in comparison with the control (epidermis which was not enhancer treated). Iontophoresis further enhanced (p < 0.05) the flux of LHRH through terpenes/EtOH treated epidermis in comparison with their passive permeability. Reversibility studies showed that the post-recovery passive flux of LHRH through 5% limonene in EtOH/iontophoresis treated epidermis was significantly (p < 0.05) decreased but did not significantly recover to the baseline flux (i.e., flux through control epidermis). The SC treated with terpenes/ EtOH showed a decrease in peak heights and areas for both asymmetric and symmetric C-H stretching absorbances in comparison to untreated SC. A greater percent decrease in peak heights and areas was obtained by limonene/EtOH. However, treatment of the SC with terpenes/EtOH followed by iontophoresis did not further decrease the percentage of peak height and area over and above terpene/EtOH suggesting that iontophoresis alone does not cause SC lipid extraction.


CONCLUSIONS
Terpenes/EtOH increased LHRH permeability by enhancing the extraction of the SC lipids. Iontophoresis synergistically enhanced the permeability of LHRH through terpenes/EtOH treated epidermis. Thus, terpenes can be used as chemical enhancers in combination with iontophoresis to enhance the transdermal delivery of peptides such as LHRH.
Bhatia
K S
KS
Department of Pharmaceutical Sciences, College of Pharmacy, North Dakota State University, Fargo 58105, USA.
Singh
J
J
D000279:Administration, Cutaneous; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D016503:Drug Delivery Systems; D004558:Electric Stimulation; D004817:Epidermis / Q000737:chemistry / Q000378:metabolism*; D000431:Ethanol; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism*; D007478:Iontophoresis; D008055:Lipids / Q000032:analysis / Q000302:isolation & purification*; D012997:Solvents; D017550:Spectroscopy, Fourier Transform Infrared; D013552:Swine; D013729:Terpenes / Q000494:pharmacology*
D008055:Lipids; D012997:Solvents; D013729:Terpenes; D007987:Gonadotropin-Releasing Hormone; D000431:Ethanol