title: Bexarotene nanocrystal-Oral and parenteral formulation development, characterization and pharmacokinetic evaluation.
abstract: Bexarotene (Targretin®) is a synthetic retinoid that selectively activates the retinoid X receptor subfamily of retinoid receptors and exhibits potent anti-tumor activity. However, the poor solubility and bioavailability limit its application. The main aim of this study is to investigate the potential of oral and parenteral nanocrystals in enhancing the bioavailability of bexarotene. In this work, the orthogonal design was used to screen the optimum stabilizers and precipitation-combined microfluidization method was employed to obtain the optimal nanocrystals. According to DSC, X-ray diffraction analysis and Raman examination, the nanocrystals were still in crystalline state after the preparation procedure. By reducing the particle size, the in vitro dissolution rate of bexarotene was increased significantly. The in vivo test was carried out in rats and pharmacokinetic parameters of the bexarotene solution and bexarotene nanocrystals were compared after gavage and intravenous administration. The higher AUC and lower Cmax indicated that oral bexarotene nanocrystals significantly increased the bioavailability of bexarotene and decreased its side effects. Compared to the oral nanocrystals, the intravenous nanocrystals cut losses and increased bioavailability because of the absence of first pass effect and enterohepatic circulation.
authors: Department of Natural Products Chemistry, Key Lab of Chemical Biology (MOE), School of Pharmaceutical Sciences, Shandong University, Jinan, PR China; Department of Pharmaceutics, School of Pharmaceutical Sciences, Liaoning University, Shenyang, PR China.
authors: Lijiang
authors: L
authors: Chen
authors: Department of Pharmaceutics, School of Pharmaceutical Sciences, Liaoning University, Shenyang, PR China.
authors: Yongjie
authors: Y
authors: Wang
authors: Department of Natural Products Chemistry, Key Lab of Chemical Biology (MOE), School of Pharmaceutical Sciences, Shandong University, Jinan, PR China.
authors: Jiaozhen
authors: J
authors: Zhang
authors: Department of Pharmaceutics, School of Pharmaceutical Sciences, Shandong University, Jinan, PR China.
authors: Leilei
authors: L
authors: Hao
authors: Department of Pharmaceutics, School of Pharmaceutical Sciences, Shandong University, Jinan, PR China.
authors: Hejian
authors: H
authors: Guo
authors: Department of Natural Products Chemistry, Key Lab of Chemical Biology (MOE), School of Pharmaceutical Sciences, Shandong University, Jinan, PR China. Electronic address: louhongxiang@sdu.edu.cn.
authors: Hongxiang
authors: H
authors: Lou
authors: Department of Pharmaceutics, School of Pharmaceutical Sciences, Shandong University, Jinan, PR China. Electronic address: zhangdianrui2006@163.com.
authors: Dianrui
authors: D
authors: Zhang
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D000077610:Bexarotene; D004337:Drug Carriers / Q000737:chemistry*; D065546:Drug Liberation; D005612:Freeze Drying; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D017208:Rats, Wistar; D047488:Retinoid X Receptors / Q000819:agonists; D012995:Solubility; D013059:Spectrum Analysis, Raman; D013499:Surface Properties; D013764:Tetrahydronaphthalenes / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D014018:Tissue Distribution
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D047488:Retinoid X Receptors; D013764:Tetrahydronaphthalenes; D000077610:Bexarotene
keywords: Bexarotene; Crystalline state; Dissolution rate; Nanocrystals; Parenteral administration; Pharmacokinetics