Effect of different enhancers on the transdermal permeation of insulin analog

• Published in: International journal of pharmaceutics Vol. 398; no. 1; pp. 83 - 92
• Main Authors: Yerramsetty, K.M., Rachakonda, V.K., Neely, B.J., Madihally, S.V., Gasem, K.A.M.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 15.10.2010; Elsevier
• Subjects: Administration, Cutaneous; Animals; Biological and medical sciences; Cells, Cultured; Drug delivery; Drug Delivery Systems - methods; General pharmacology; Humans; Insulin; Insulin - administration & dosage; Insulin - analogs & derivatives; Insulin - chemistry; Insulin - metabolism; Insulin Lispro; Male; Medical sciences; Permeation enhancer; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Random Allocation; Skin Absorption - drug effects; Skin Absorption - physiology; Swine; Transdermal; Drug delivery; Transdermal; Permeation enhancer; Insulin; Pharmaceutical technology; Analog; Permeation; Drug carrier; Absorption enhancer; Percutaneous route
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2010.07.029

Using chemical penetration enhancers (CPEs), transdermal drug delivery (TDD) offers an alternative route for insulin administration, wherein the CPEs reversibly reduce the barrier resistance of the skin. However, there is a lack of sufficient information concerning the effect of CPE chemical structure on insulin permeation. To address this limitation, we examined the effect of CPE functional groups on the permeation of insulin. A virtual design algorithm that incorporates quantitative structure–property relationship (QSPR) models for predicting the CPE properties was used to identify 43 potential CPEs. This set of CPEs was pre-screened using a resistance technique, and the 22 best CPEs were selected. Next, standard permeation experiments in Franz cells were performed to quantify insulin permeation. Our results indicate that specific functional groups are not directly responsible for enhanced insulin permeation. Rather, permeation enhancement is produced by molecules that exhibit positive log K ow values and possess at least one hydrogen donor or acceptor. Toluene was the only exception among the 22 potential CPEs considered. In addition, toxicity analyses of the 22 CPEs were performed. A total of eight CPEs were both highly enhancing (permeability coefficient at least four times the control value) and non-toxic, five of which are new discoveries.