title: A novel glyceryl monoolein-bearing cubosomes for gambogenic acid: Preparation, cytotoxicity and intracellular uptake.
abstract: Lyotropic cubic liquid crystalline nanoparticles, also known as 'cubosomes', have been tested as effective carriers for a variety of drugs due to their ability to enhance delivery efficiency and reduced drug side effects. Cubosomes are colloidal carriers composed of biodegradable Glyceryl monooleate and F127. Being composed of well tolerable and physiological materials, these carriers are well tolerated, compatible and non-toxic. In this study, therefore, we developed a novel, water-soluble, glyceryl monooleate and F127 based multiblock copolymer for Gambogenic acid (GNA) by emulsion-evaporation and low temperature-solidification technique. Physicochemical properties, in vitro cytotoxicity, cellular uptake and in vivo pharmacokinetic of GNA-loaded cubosomes (GNA-Cubs) were investigated. The results revealed that GNA-Cubs were spherical or ellipsoidal monocellular by dynamic light scattering, meanwhile, 150-250nm in mean size with narrow polydispersity indexas determined by transmission electron microscopy. Small angle X-ray scattering indicated that GNA-Cubs retain the Pn3m cubic symmetry. Compared with GNA solution, GNA-Cubs exhibited markedly prolonged inhibitory activity in SMMC-7721 cells, as well as time-dependent increases in intra-cellular uptake. Furthermore, in vivo pharmacokinetic study showed that the Cmax values and the AUC of GNA-Cubs were higher than GNA solution approximately 1.2-fold and 9.1-fold, respectively. In conclusion, the results showed that the cubic liquid crystalline nanoparticles could be a potentially nanocarrier in the delivery of GNA for cancer therapy.
authors.affiliation: Pharmacokinetics Lab, Anhui University of Chinese Medicine, Hefei 230031, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Luo
authors.affiliation: Pharmacokinetics Lab, Anhui University of Chinese Medicine, Hefei 230031, China.
authors.forename: Tongyuan
authors.initials: T
authors.lastname: Lin
authors.affiliation: Pharmacokinetics Lab, Anhui University of Chinese Medicine, Hefei 230031, China.
authors.forename: Cai Yuan
authors.initials: CY
authors.lastname: Zhang
authors.affiliation: Pharmacokinetics Lab, Anhui University of Chinese Medicine, Hefei 230031, China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Zhu
authors.affiliation: Pharmacokinetics Lab, Anhui University of Chinese Medicine, Hefei 230031, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.affiliation: Pharmacokinetics Lab, Anhui University of Chinese Medicine, Hefei 230031, China.
authors.forename: Zhaojie
authors.initials: Z
authors.lastname: Ji
authors.affiliation: Pharmacokinetics Lab, Anhui University of Chinese Medicine, Hefei 230031, China.
authors.forename: Buyun
authors.initials: B
authors.lastname: Jia
authors.affiliation: Pharmacokinetics Lab, Anhui University of Chinese Medicine, Hefei 230031, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Ge
authors.affiliation: Pharmacokinetics Lab, Anhui University of Chinese Medicine, Hefei 230031, China. Electronic address: pengdy@ahtcm.com.
authors.forename: Daiyin
authors.initials: D
authors.lastname: Peng
authors.affiliation: Pharmacokinetics Lab, Anhui University of Chinese Medicine, Hefei 230031, China. Electronic address: anzhongdong@126.com.
authors.forename: Weidong
authors.initials: W
authors.lastname: Chen
mesh_terms: D018929:Cell Culture Techniques; D002470:Cell Survival; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D002851:Chromatography, High Pressure Liquid; D003102:Colloids / Q000737:chemistry; D016503:Drug Delivery Systems; D065546:Drug Liberation; D004705:Endocytosis; D005989:Glycerides / Q000737:chemistry*; D050866:Liquid Crystals; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D011095:Polyethylenes; D011126:Polypropylenes; D014966:Xanthenes / Q000737:chemistry*
chemical_list: D003102:Colloids; D005989:Glycerides; D011095:Polyethylenes; D011126:Polypropylenes; D014966:Xanthenes; C078661:UCON 50-HB-5100; C045863:neo-gambogic acid; C005953:monoolein
keywords: Cellular uptake; Cubosomes; Gambogenic acid; Glyceryl monooleate/pluronic F127