title: Enhancing in vivo Bioavailability in Beagle Dogs of GLM-7 as a Novel Anti-Leukemia Drug through a Self-Emulsifying Drug Delivery System for Oral Delivery.
abstract: GLM-7 is a novel anti-leukemia drug in the pre-clinical study. The previous study shows that GLM-7 is a poorly water-soluble drug with low oral bioavailability. In this study, we employed the self-emulsifying drug delivery system (SEDDS) to improve the oral bioavailability of GLM-7. The GLM-7 SEDDS formulation was prepared using MCT as oil, ovolecithin as surfactant and Transcutol as co-surfactant, and the formulation parameters were optimized by the response surface methodology. The optimized GLM-7 SEDDS formulation showed a stable liquid state, and can automatically emulsify to form the isotropic emulsion once exposure to the water phase. The generated emulsion showed the spherical shape, and had an average size of about 399 nm and a zeta potential of about -42 mV. Compared to the GLM-7 dissolution less than 1.4% from pure GLM-7 powder (reference), the GLM-7 SEDDS formulation could remarkably enhance the in vitro dissolution to 83% in the medium of 0.1N HCL. The in vivo oral bioavailability of GLM-7 SEDDS formulation was investigated in beagle dogs. The results demonstrated that the GLM-7 SEDDS formulation significantly enhanced the plasma concentrations of GLM-7, and the Cmax reached to 878 ng/ml and was 9.2 folds as high as the Cmax 95.85 ng/ml of reference. Moreover, the area under the curve (AUC) of GLM-7 SEDDS formulation was 13.6 times higher than that of reference, which suggested that the SEDDS formulation remarkably increased the oral bioavailability of GLM-7.
authors.forename: Yuli
authors.initials: Y
authors.lastname: Wang
authors.forename: Ning
authors.initials: N
authors.lastname: Yu
authors.forename: Rui
authors.initials: R
authors.lastname: Guo
authors.forename: Meiyan
authors.initials: M
authors.lastname: Yang
authors.forename: Li
authors.initials: L
authors.lastname: Shan
authors.forename: Wei
authors.initials: W
authors.lastname: Huang
authors.forename: Wei
authors.initials: W
authors.lastname: Gong
authors.forename: Shuai
authors.initials: S
authors.lastname: Shao
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Chen
authors.affiliation: State key Laboratory of Toxicology and Medical Countermeasures, Department of Pharmaceutics, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China. gaocs@bmi.ac.cn.
authors.forename: Chunsheng
authors.initials: C
authors.lastname: Gao
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000493:pharmacokinetics* / Q000494:pharmacology; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical / Q000379:methods; D004285:Dogs; D016503:Drug Delivery Systems / Q000379:methods; D045703:Emulsifying Agents / Q000737:chemistry; D004655:Emulsions / Q000737:chemistry* / Q000493:pharmacokinetics* / Q000494:pharmacology; D007938:Leukemia / Q000188:drug therapy*; D010316:Particle Size; D012995:Solubility; D013501:Surface-Active Agents / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D045703:Emulsifying Agents; D004655:Emulsions; D013501:Surface-Active Agents