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Isfahan University of Medical Sciences
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Document Type
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Latin Dissertation
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Language of Document
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English
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Record Number
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102529
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Doc. No
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T8485
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Call number
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QV,785,P226m,2003
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Main Entry
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Pardakhty, Abbas
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Title & Author
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Niosomes as novel insulin oral delivery systems
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College
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Schools, Pharmacy
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Date
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, 2003
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Degree
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P.HD
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Page No
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XII, 172 p.
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Note
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This thesis is also persented as a research procject with project ID 79223
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Abstract
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Introduction: Protein drugs are undertaken proteolytic enzyme degradation and poor oral absorption. The aim of this research was to formulate non-ionic surfactant vesicles, niosomes, for oral delivery of insulin as a model protein drug, Non-ionic surfactants are more stable against oxidation and temperature in comparison with phospholipids, the main constituent of liposomes. Methods: The ability of 15 different compounds from Brij'`', Spam and TweeniM non-ionic surfactants with or without cholesterol, to form vesicles was investigated by optical microscopy, following classic film hydration method of vesicle preparation. In the presence of optimum molar ratio of cholesterol, the best formulations were studied for insulin encapsulation. The release of insulirt from niosomes in SGF and SIF and the protection of insulin against pepsin, a-chymotrypsin and trypsin were investigated in vitro. Finally, pharmacological parameters of drug, following intragastric administration of 100 lU/kg noisome-encapsulated insulin in Brij 52, Brij 93 and Span 60 niosome formulations in diabetic rats were obtained. Results: Brij and Span surfactants with maximum HLB of 12.4 formed stable niosomes_ The size of vesicles, measured by static laser light scattering technique, was influenced by cholesterol, dicetyiphosphate (DCP) and HLB of surfactant contents. Insulin encapsulation efficiencies of niosomes were between i $ to 41.5 percents. Encapsulation of insulin in niosomes often showed a significant protection against proteolytic enzymes. Gel slate vesicles demonstrated slower release rate of insulin in both SGF and SW. Area above blood glucose concentration (AACrj..z min) and area under insulin concentration (AUC0-2so m;n) of Brij 92 niosomes were 5.95 x 10` percent min and 23.46x10` uU.ml',min, respectively. This shows the capability of using niosornes in oral delivery of insulin. Discussion: Encapsulation of insulin was achieved in different new drug delivery systems such as liposomes, nanocapsules, enzyme protected capsules to protect protein from destructive effects of GI tract enzymes. In this study non-ionic surfactant vesicles were used for this purpose. Niosome-encapsulated insulin can be protected from degrading enzymes, but low relative bioavailability of this drug in diabetic rats may berelated to high molecular size of hexanieric insulin. However a very good obtained correlation (r2 0.913) between AACm2SO min and in vitro a-chymotrypsin protection can be used for more studies in future investigations..
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Descriptor
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1. Drug delivery system.- descriptors: Drug delivery systems
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Insulin
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Liposomes
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Proteins
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Enzymes
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Diabetes Mellitus
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Added Entry
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Family, Name
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Varshosaz, Jaleh
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Haj Hashemi, Vali-Olah, Rouholamini, Abdolhossein
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Translated Title Supplied by Cataloguer
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استفاده از نیوزومها برای دارورسانی خوراکی انسولین
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http://elib.mui.ac.ir/site/catalogue/102529
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