Maestrelli Francesca, Mura Paola, González-Rodríguez María Luisa, Cózar-Bernal María José, Rabasco Antonio María, Di Cesare Mannelli Lorenzo, Ghelardini Carla
Department of Chemistry, University of Florence, via Schiff 6, Sesto Fiorentino, 50019 Florence, Italy.
Department of Chemistry, University of Florence, via Schiff 6, Sesto Fiorentino, 50019 Florence, Italy.
Int J Pharm. 2017 Sep 15;530(1-2):430-439. doi: 10.1016/j.ijpharm.2017.07.083. Epub 2017 Aug 1.
Metformin is an oral hypoglycemic agent used in the type 2 diabetes, whose poor bioavailability and short half-life make the development of effective extended-release formulations highly desirable. Different metformin-loaded chitosomal and niosomal formulations were developed and suitably characterized, but were unable to provide the desired sustained release. The entrapment of both kinds of colloidal dispersions in calcium alginate beads enabled to strongly reduce the amount of drug released at gastric level (from 18 up to a maximum of 30%), and to obtain a sustained release in simulated intestinal fluid, which was properly tuned by varying the percentage of calcium alginate in the beads. In vivo studies on rats revealed a significant improvement of metformin hypoglycemic effect when orally administered as chitosomal and even more as niosomal dispersion entrapped in alginate beads, not only with respect to the drug as such, but also to the alginate beads loaded with the plain drug. The more intense and sustained therapeutic effect with time provided by the drug-in niosomes-in alginate bead formulation could be very profitable for maintaining tight blood glucose levels over prolonged period of time after oral administration, allowing a reduction of its dose and related collateral effects, and improving patient compliance.
二甲双胍是一种用于治疗2型糖尿病的口服降糖药，其生物利用度低、半衰期短，因此开发有效的缓释制剂非常必要。人们研发了不同的载二甲双胍壳聚糖体和囊泡体剂型并对其进行了适当表征，但这些剂型无法实现预期的缓释效果。将这两种胶体分散体包封在海藻酸钙珠粒中，能够大幅减少在胃部释放的药物量（从18%降至最高30%），并在模拟肠液中实现缓释，通过改变珠粒中海藻酸钙的百分比可对缓释效果进行适当调节。对大鼠的体内研究表明，当以壳聚糖体形式口服给药时，二甲双胍的降糖效果有显著改善，而以囊泡体分散体包封在海藻酸钙珠粒中的形式给药时，降糖效果更佳，不仅相对于药物本身，而且相对于装载普通药物的海藻酸钙珠粒而言都是如此。载于囊泡体中的药物包封在海藻酸钙珠粒中所产生的随时间更强烈且持续的治疗效果，对于口服给药后长时间维持严格的血糖水平可能非常有益，可减少药物剂量及其相关副作用，并提高患者的依从性。
