title: Hypoglycaemic effect of a novel insulin buccal formulation on rabbits.
abstract: Transmucosal delivery is a suitable route for insulin non-injection administration. In this study, the hypoglycaemic effect of INSULIN BUCCAL SPRAY (IBS), a formulation with soybean lecithin and propanediol combined as absorption enhancer for insulin on diabetic rabbits and rats, were investigated. The hypoglycaemic rate was calculated and the pharmacodynamics and pharmacokinetics of the formulation in rabbits were studied. The results show that when the diabetic rabbits were administrated with IBS in dosages of 0.5, 1.5 and 4.5Ukg(-1), the blood glucose level decreased significantly compared with that of the control group and the hypoglycaemic effect lasted over 5h. The blood glucose decreasing rates are 22.4, 48.1 and 53.5%, respectively. The average bioavailability of IBS by buccal delivery versus subcutaneous injection is 29.2%. Meanwhile, the diabetic rats were administrated with IBS in dosages of 1.0, 3.0 and 9.0Ukg(-1), the blood glucose level decreased significantly compared with that of the control group and the hypoglycaemic effect lasted over 4h. The blood glucose decreasing rates are 24.6, 47.5 and 59.6%, respectively. Furthermore, the penetration of fluorescein isothiocyanate (FITC)-labelled insulin through rabbit buccal mucosa was investigated by scanning the distribution of the fluorescent probe in the epithelium using confocal laser scanning microscopy. The results revealed that FITC-insulin can pass through the buccal mucosa promoted by the enhancer and the passage of insulin across the epithelium includes both intracellular and paracellular routes. From the rabbit and rat experimental results showed that IBS is an effective buccal delivery system, which is promising for clinical trial and the future clinical application.
authors.affiliation: Institute of Pharmacy, Huazhong University of Science & Technology, 430074 Wuhan, PR China. hbxu@mail.hust.edu.cn
authors.forename: Hui-Bi
authors.initials: HB
authors.lastname: Xu
authors.forename: Kai-Xun
authors.initials: KX
authors.lastname: Huang
authors.forename: Yu-Shan
authors.initials: YS
authors.lastname: Zhu
authors.forename: Qiu-Hua
authors.initials: QH
authors.lastname: Gao
authors.forename: Qing-Zhi
authors.initials: QZ
authors.lastname: Wu
authors.forename: Wei-Qun
authors.initials: WQ
authors.lastname: Tian
authors.forename: Xi-Qun
authors.initials: XQ
authors.lastname: Sheng
authors.forename: Ze-Xian
authors.initials: ZX
authors.lastname: Chen
authors.forename: Zhong-Hong
authors.initials: ZH
authors.lastname: Gao
mesh_terms: D000278:Administration, Buccal; D000327:Adsorption; D000818:Animals; D019540:Area Under Curve; D001682:Biological Availability; D001786:Blood Glucose / Q000032:analysis / Q000187:drug effects*; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000378:metabolism*; D005079:Excipients / Q000737:chemistry; D005260:Female; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D007328:Insulin / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D008297:Male; D009061:Mouth Mucosa / Q000378:metabolism; D010713:Phosphatidylcholines / Q000737:chemistry; D011409:Propylene Glycols / Q000737:chemistry; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D001786:Blood Glucose; D005079:Excipients; D007004:Hypoglycemic Agents; D007328:Insulin; D010713:Phosphatidylcholines; D011409:Propylene Glycols