Development, optimization and biological evaluation of chitosan scaffold formulations of new xanthine derivatives for treatment of type-2 diabetes mellitus

作者：Lupascu Florentina Geanina; Dash Mamoni; Samal Sangram Keshari; Dubruel Peter; Lupusoru Catalina Elena; Lupusoru Raoul Vasile; Dragostin Oana; Profire Lenuta^*

来源：European Journal of Pharmaceutical Sciences, 2015, 77: 122-134.

DOI：10.1016/j.ejps.2015.06.008

• Diabetes mellitus
• Chitosan
• Microparticles
• Xanthine derivative
• Drug delivery

New xanthine derivatives as antidiabetic agents were synthesized and new chitosan formulations have been developed in order to improve their biological and pharmacokinetic profile. Their physicochemical properties in terms of particle size, morphology, swelling degree, crystalline state, the loading efficiency as well as in vitro release and biodegradation rate were evaluated. According to the results the optimized formulations have a high drug loading efficiency (more than 70%), small particle size, a good release profile in the simulated biological fluids (the percentage of cumulative release being more than 55%) and improved biodegradation rate in reference with chitosan microparticles. The presence of xanthine derivatives (6, 7) in chitosan microparticles was demonstrated by means of FIR analysis. The X-ray diffraction (XRD) proved that xanthine derivatives present a crystalline state. The biological evaluation assays confirmed the antioxidant and antidiabetic effects of the xanthine derivatives (6, 7) and their chitosan formulations (CS-6, CS-7). Xanthine derivative 6 showed a high antiradical scavenging effect (DPPH remaining = 41.78%). It also reduced the glucose blood level with 59.30% and recorded level of glycosylated hemoglobin was 4.53%. The effect of its chitosan formulation (CS-6) on the level of blood glucose (114.5 mg/dl) was even more intense than the one recorded by pioglitazone (148.5 mg/dl) when used as standard antidiabetic drug. These results demonstrated the potential application of xanthine derivative 6 and its chitosan formulation (CS-6) in the treatment of the diabetes mellitus syndrome.

• 出版日期2015-9-18