title: Development, optimization and biological evaluation of chitosan scaffold formulations of new xanthine derivatives for treatment of type-2 diabetes mellitus.
abstract: 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 FTIR 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 (114.5mg/dl) was even more intense than the one recorded by pioglitazone (148.5mg/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.
authors.affiliation: University of Medicine and Pharmacy "Grigore T. Popa", Faculty of Pharmacy, University 16, 700115 Iasi, Romania. Electronic address: lupascu.geanina@yahoo.com.
authors.forename: Florentina Geanina
authors.initials: FG
authors.lastname: Lupascu
authors.affiliation: Polymer Chemistry & Biomaterials Research Group, Ghent University, Krijgslaan 281, S4-Bis, B-9000 Ghent, Belgium. Electronic address: mamoni.dash@ugent.be.
authors.forename: Mamoni
authors.initials: M
authors.lastname: Dash
authors.affiliation: Laboratory of General Biochemistry and Physical Pharmacy, Centre for Nano- and Biophotonics, Ghent University, Ottergemsesteenweg 460, 9000 Ghent, Belgium. Electronic address: sangramkeshari.samal@ugent.be.
authors.forename: Sangram Keshari
authors.initials: SK
authors.lastname: Samal
authors.affiliation: Polymer Chemistry & Biomaterials Research Group, Ghent University, Krijgslaan 281, S4-Bis, B-9000 Ghent, Belgium. Electronic address: peter.dubruel@ugent.be.
authors.forename: Peter
authors.initials: P
authors.lastname: Dubruel
authors.affiliation: University of Medicine and Pharmacy "Grigore T. Popa", Faculty of Medicine, University 16, 700115 Iasi, Romania. Electronic address: celupusoru@yahoo.com.
authors.forename: Catalina Elena
authors.initials: CE
authors.lastname: Lupusoru
authors.affiliation: University of Medicine and Pharmacy "Grigore T. Popa", Faculty of Medicine, University 16, 700115 Iasi, Romania. Electronic address: rvlupusoru@yahoo.com.
authors.forename: Raoul-Vasile
authors.initials: RV
authors.lastname: Lupusoru
authors.affiliation: University of Medicine and Pharmacy "Grigore T. Popa", Faculty of Pharmacy, University 16, 700115 Iasi, Romania. Electronic address: oana.dragostin@umfiasi.ro.
authors.forename: Oana
authors.initials: O
authors.lastname: Dragostin
authors.affiliation: University of Medicine and Pharmacy "Grigore T. Popa", Faculty of Pharmacy, University 16, 700115 Iasi, Romania. Electronic address: lenuta.profire@umfiasi.ro.
authors.forename: Lenuta
authors.initials: L
authors.lastname: Profire
mesh_terms: D000818:Animals; D048271:Chitosan / Q000737:chemistry*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004337:Drug Carriers; D004353:Drug Evaluation, Preclinical; D007004:Hypoglycemic Agents / Q000737:chemistry* / Q000627:therapeutic use; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D017550:Spectroscopy, Fourier Transform Infrared; D014961:X-Ray Diffraction; D014970:Xanthines / Q000737:chemistry* / Q000627:therapeutic use
chemical_list: D004337:Drug Carriers; D007004:Hypoglycemic Agents; D014970:Xanthines; D048271:Chitosan
keywords: Chitosan; Diabetes mellitus; Drug delivery; Microparticles; Xanthine derivative