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Nanocomplexes of an insulinotropic drug: optimization, microparticle formation, and antidiabetic activity in rats

Authors Elmowafy E, Osman R, El-Shamy AH, Awad G

Received 27 April 2014

Accepted for publication 12 June 2014

Published 18 September 2014 Volume 2014:9(1) Pages 4449—4465


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Enas Elmowafy, Rihab Osman, Abdel Hameed El-Shamy,† Gehanne AS Awad

Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt

†Abdel Hameed El-Shamy passed away on August 25, 2013

Abstract: The aim of the present work was to test the ability of two non-diabetogenic ­carbohydrates to intranasally deliver the insulinotropic drug repaglinide (REP) for controlling blood glucose level. REP was loaded onto chitosan/alginate nanocomplexes (NCs) suitable for mucosal delivery and uptake. Improved stability and delivery characteristics were obtained by spray drying the selected NCs, yielding microparticles. A statistical experimental design was adopted to investigate the effects of the formulations’ variables on two critical responses: NC size and drug entrapment efficiency. Physicochemical characterizations of the network’s structures were done, and in vitro cytotoxicity and histopathological studies were conducted. The potential of the developed system to prolong the drug effect was tested on diabetic rats. The results showed that to attain particles suitable for nasal delivery, alginate should be used at its lowest level used in this study (0.6 mg/mL). A low level of chitosan (0.5 mg/mL) was needed when the drug was cation-loaded, while the high chitosan level (1 mg/mL) was more suitable when REP was anion-loaded. The best entrapment efficiency was achieved at a theoretical drug loading of 0.025 mg/mL. Discrete NCs could be rapidly recovered from the spray-dried microparticles. The cytotoxicity and histopathological studies indicated that such formulations were well tolerated. The antihyperglycemic activity of the nasally administered formulae was gradual but was significantly sustained over 24 hours, suggesting NC mucosal uptake. Nasal delivery of such dry powders achieved better glycemic control compared with the conventional oral tablets.

Keywords: nanocomplexes, microparticles, spray drying, nasal delivery, antidiabetic effect

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