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Iontophoretic transdermal delivery o...

Rastogi, Sumeet K.

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Iontophoretic transdermal delivery of peptides: Leuprolide acetate and insulin.

Record Type:	Electronic resources : Monograph/item
Title/Author:	Iontophoretic transdermal delivery of peptides: Leuprolide acetate and insulin./
Author:	Rastogi, Sumeet K.
Description:	214 p.
Notes:	Source: Dissertation Abstracts International, Volume: 65-04, Section: B, page: 1801.
Contained By:	Dissertation Abstracts International65-04B.
Subject:	Health Sciences, Pharmacy. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3129101
ISBN:	049676361X

Iontophoretic transdermal delivery of peptides: Leuprolide acetate and insulin.
Rastogi, Sumeet K.

Iontophoretic transdermal delivery of peptides: Leuprolide acetate and insulin. - 214 p.

Source: Dissertation Abstracts International, Volume: 65-04, Section: B, page: 1801.

Thesis (Ph.D.)--North Dakota State University, 2004.

The effect of chemical enhancers (e.g., alkyl acetates, fatty acids, limonene, and depilatory lotions) and iontophoresis was investigated on the in vitro permeability of leuprolide acetate and insulin through porcine epidermis. Biophysical changes in the stratum corneum (SC) lipids and proteins by chemical enhancers/iontophoresis were studied by Fourier transform infrared spectroscopy. The composition of the epidermal lipids and fatty acids extracted by different enhancer treatments was measured by thin layer chromatography and gas chromatography, respectively. In vivo studies were undertaken to investigate the effect of iontophoresis in combination with chosen chemical enhancers on the percutaneous absorption of insulin and blood glucose lowering in diabetic New Zealand white (NZW) rabbits. Skin barrier function and primary skin irritation were evaluated. In vitro transepidermal transport of leuprolide acetate and insulin was synergistically enhanced (p < 0.05) by chemical enhancers (alkyl acetates, fatty acids, and limonene) and iontophoresis due to SC lipid extraction. The decrease in alpha-helical conformations and increase in the unordered conformations of SC protein in combination with lipid extraction of the SC are suggested to be the primary reasons for the increase in the passive and iontophoretic permeabilities of leuprolide acetate and insulin through the depilatory lotion treated epidermis. The three major groups of lipids contributing to the extracted lipids were ceramides, phospholipids, and cholesterol. Linoleic acid showed greater percentage loss among all the fatty acids extracted from the SC. Different enhancers (i.e., linolenic acid, limonene, and Better OffRTM) in combination with iontophoresis decreased the blood glucose levels to a varying extent in alloxan-induced NZW diabetic rabbits. A decrease in blood glucose level was corroborated with an increase in serum insulin level for different pretreatments. Transepidermal water loss and skin capacitance studies indicate skin barrier function perturbation due to chemical enhancer and iontophoresis in the NZW rabbits. There was no primary skin irritation in rabbits due to the chemical enhancers and iontophoresis. In conclusion, iontophoresis in combination with enhancers significantly (p < 0.05) increased the in vitro percutaneous absorption of the peptides (leuprolide acetate and insulin), and the changes brought by iontophoresis/enhancer in the barrier properties of the skin in vivo were reversible.

ISBN: 049676361XSubjects--Topical Terms:

1017737
Health Sciences, Pharmacy.

Iontophoretic transdermal delivery of peptides: Leuprolide acetate and insulin.
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500 $a Major Professor: Jagdish Singh.
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520 $a The effect of chemical enhancers (e.g., alkyl acetates, fatty acids, limonene, and depilatory lotions) and iontophoresis was investigated on the in vitro permeability of leuprolide acetate and insulin through porcine epidermis. Biophysical changes in the stratum corneum (SC) lipids and proteins by chemical enhancers/iontophoresis were studied by Fourier transform infrared spectroscopy. The composition of the epidermal lipids and fatty acids extracted by different enhancer treatments was measured by thin layer chromatography and gas chromatography, respectively. In vivo studies were undertaken to investigate the effect of iontophoresis in combination with chosen chemical enhancers on the percutaneous absorption of insulin and blood glucose lowering in diabetic New Zealand white (NZW) rabbits. Skin barrier function and primary skin irritation were evaluated. In vitro transepidermal transport of leuprolide acetate and insulin was synergistically enhanced (p < 0.05) by chemical enhancers (alkyl acetates, fatty acids, and limonene) and iontophoresis due to SC lipid extraction. The decrease in alpha-helical conformations and increase in the unordered conformations of SC protein in combination with lipid extraction of the SC are suggested to be the primary reasons for the increase in the passive and iontophoretic permeabilities of leuprolide acetate and insulin through the depilatory lotion treated epidermis. The three major groups of lipids contributing to the extracted lipids were ceramides, phospholipids, and cholesterol. Linoleic acid showed greater percentage loss among all the fatty acids extracted from the SC. Different enhancers (i.e., linolenic acid, limonene, and Better OffRTM) in combination with iontophoresis decreased the blood glucose levels to a varying extent in alloxan-induced NZW diabetic rabbits. A decrease in blood glucose level was corroborated with an increase in serum insulin level for different pretreatments. Transepidermal water loss and skin capacitance studies indicate skin barrier function perturbation due to chemical enhancer and iontophoresis in the NZW rabbits. There was no primary skin irritation in rabbits due to the chemical enhancers and iontophoresis. In conclusion, iontophoresis in combination with enhancers significantly (p < 0.05) increased the in vitro percutaneous absorption of the peptides (leuprolide acetate and insulin), and the changes brought by iontophoresis/enhancer in the barrier properties of the skin in vivo were reversible.
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