title: Studies on the preparation, characterization and pharmacokinetics of Amoitone B nanocrystals.
abstract: Amoitone B, as a new derivative of cytosporone B, has been proved to be a natural agonist for Nur77. It exhibits remarkable anticancer activity in vivo and has the potential to be a therapeutic agent for cancer treatment. However, the poor solubility and dissolution rate result in low therapeutic index for injection and low bioavailability for oral administration, therefore limiting its application. In order to magnify the clinical use of Amoitone B, nanocrystal was selected as an application technology to solve the above problems. In this study, the optimized Amoitone B nanocrystals with small and uniform particle size were successfully prepared by microfluidization method and investigated by morphology, size distribution, and zeta potential. The differential scanning calorimetry (DSC) and X-ray diffraction (XRD) confirmed there was no crystalline state changed in the size reduction process. For Amoitone B nanocrystals, an accelerated dissolution velocity and increased saturation solubility were achieved in vitro and a markedly different pharmacokinetic property in vivo was exhibited with retarded clearance and magnified AUC compared with Amoitone B solution. These results implied that developing Amoitone B as nanocrystals is a promising choice for intravenous delivery and further application for cancer therapy.
authors.affiliation: Department of Pharmaceutics, College of Pharmacy, Shandong University, 44 Wenhua Xilu, Jinan 250012, PR China.
authors.forename: Leilei
authors.initials: L
authors.lastname: Hao
authors.forename: Xiaoyong
authors.initials: X
authors.lastname: Wang
authors.forename: Dianrui
authors.initials: D
authors.lastname: Zhang
authors.forename: Qingyan
authors.initials: Q
authors.lastname: Xu
authors.forename: Siyang
authors.initials: S
authors.lastname: Song
authors.forename: Feihu
authors.initials: F
authors.lastname: Wang
authors.forename: Caiyun
authors.initials: C
authors.lastname: Li
authors.forename: Hejian
authors.initials: H
authors.lastname: Guo
authors.forename: Yue
authors.initials: Y
authors.lastname: Liu
authors.forename: Dandan
authors.initials: D
authors.lastname: Zheng
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D019540:Area Under Curve; D001682:Biological Availability; D002152:Calorimetry, Differential Scanning; D003460:Crystallization; D004339:Drug Compounding / Q000379:methods; D044085:Microfluidics; D053758:Nanoparticles; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1 / Q000819:agonists; D010316:Particle Size; D010648:Phenylacetates / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D011817:Rabbits; D012995:Solubility; D013678:Technology, Pharmaceutical / Q000379:methods; D014961:X-Ray Diffraction
chemical_list: D000970:Antineoplastic Agents; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D010648:Phenylacetates; C576231:n-amyl 2-(3,5-dihydroxy-2-(1-nonanoyl)phenyl)acetate