Golocorbin-Kon Svetlana, Calasan Jelena, Milijasevic Boris, Vukmirovic Sasa, Lalic-Popovic Mladena, Mikov Momir, Al-Salami Hani
Department of Pharmacy, Faculty of Medicine, University of Novi Sad, Hajduk Veljkova 3, 21000, Novi Sad, Serbia.
Chair of Nutrition and Immunology, TUM School of Life Sciences Weihenstephan, Technical University of Munich, Munich, Germany.
Eur J Drug Metab Pharmacokinet. 2017 Dec;42(6):1005-1011. doi: 10.1007/s13318-017-0415-0.
Gliclazide is a drug commonly used in type 2 diabetes mellitus. Recently, gliclazide has shown desirable pharmacological effects such as immunoregulatory and anti-clotting effects, which suggests potential applications in type 1 diabetes mellitus (T1DM). Gliclazide has variable absorption after oral administration, and thus using targeted-delivery techniques, such as microencapsulation, may optimise gliclazide absorption and potential applications in T1DM. Bile acids such as cholic acid have shown microcapsule-stabilising and controlled-release effects, and thus their incorporation into gliclazide microcapsules may further optimise gliclazide release, absorption and antidiabetic effects. Accordingly, this study aimed to examine the hypoglycaemic effects of gliclazide microcapsules with and without cholic acid, in a rat model of T1DM.
Thirty-five alloxan-induced T1DM rats were randomly divided into five equal groups and gavaged a single dose of empty microcapsules, gliclazide, gliclazide microcapsules, gliclazide-cholic acid or gliclazide-cholic acid microcapsules. Blood samples were collected over 10 h post-dose and analysed for blood glucose and gliclazide serum concentrations.
Gliclazide microcapsules exerted a hypoglycaemic effect in the diabetic rats, and cholic acid incorporation diminished the hypoglycaemic effects, which suggests the lack of synergistic effects between gliclazide and cholic acid. In addition, neither microencapsulation nor cholic acid incorporation optimised gliclazide absorption which suggests that hypoglycaemic effects of gliclazide are independent of its absorption and serum concentrations. This also suggests that hypoglycaemic effects of gliclazide may be associated with gut-metabolic activation rather than gut-targeted delivery and systemic absorption.
Gliclazide microcapsules exerted hypoglycaemic effects in T1DM rats independent of insulin and thus may have potentials in treatment of T1DM.
格列齐特是2型糖尿病常用药物。最近，格列齐特显示出如免疫调节和抗凝血等理想的药理作用，这表明其在1型糖尿病（T1DM）中具有潜在应用价值。格列齐特口服后吸收情况不一，因此采用微囊化等靶向给药技术可能会优化格列齐特的吸收及其在T1DM中的潜在应用。胆酸如胆酸已显示出微囊稳定和控释作用，因此将其纳入格列齐特微囊中可能会进一步优化格列齐特的释放、吸收及抗糖尿病作用。因此，本研究旨在检测含胆酸和不含胆酸的格列齐特微囊在T1DM大鼠模型中的降血糖作用。
将35只四氧嘧啶诱导的T1DM大鼠随机分为五组，每组数量相等，分别灌胃单剂量的空白微囊、格列齐特、格列齐特微囊、格列齐特 - 胆酸或格列齐特 - 胆酸微囊。给药后10小时内采集血样，分析血糖和格列齐特血清浓度。
格列齐特微囊对糖尿病大鼠有降血糖作用，而加入胆酸会减弱降血糖作用，这表明格列齐特和胆酸之间缺乏协同作用。此外，微囊化和加入胆酸均未优化格列齐特的吸收，这表明格列齐特的降血糖作用与其吸收和血清浓度无关。这也表明格列齐特的降血糖作用可能与肠道代谢激活有关，而非肠道靶向给药和全身吸收。
格列齐特微囊在T1DM大鼠中发挥了独立于胰岛素的降血糖作用，因此在T1DM治疗中可能具有潜力。
