title: Nanocomplexes of an insulinotropic drug: optimization, microparticle formation, and antidiabetic activity in rats.
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.
authors.affiliation: Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt.
authors.forename: Enas
authors.initials: E
authors.lastname: Elmowafy
authors.affiliation: Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt.
authors.forename: Rihab
authors.initials: R
authors.lastname: Osman
authors.affiliation: Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt.
authors.forename: Abdel Hameed
authors.initials: AH
authors.lastname: El-Shamy
authors.affiliation: Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt.
authors.forename: Gehanne As
authors.initials: GA
authors.lastname: Awad
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D002219:Carbamates / Q000008:administration & dosage* / Q000737:chemistry; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy*; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry*; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000737:chemistry; D008297:Male; D008863:Microspheres; D009297:Nasal Mucosa / Q000187:drug effects; D010880:Piperidines / Q000008:administration & dosage* / Q000737:chemistry; D017208:Rats, Wistar
chemical_list: D001786:Blood Glucose; D002219:Carbamates; D004337:Drug Carriers; D007004:Hypoglycemic Agents; D010880:Piperidines; C072379:repaglinide
keywords: antidiabetic effect; microparticles; nanocomplexes; nasal delivery; spray drying