title: Nanoformulation of dual bexarotene-tailed phospholipid conjugate with high drug loading.
abstract: Bexarotene (Bex), a synthetic retinoid X receptor-selective activator, has been proved to be an efficacious chemotherapeutic agent. But, its clinical application is limited due to the poor solubility. In this report, dual bexarotene-tailed phospholipid (DBTP) conjugate based nanovesicles were prepared in order to develop new nanoformulation. DBTP conjugate was first synthesized by conjugating two Bex molecules with glycerophosphorylcholine (GPC) through facial esterification. The amphiphilic DBTP nanovesicles were prepared without any additive by reverse-phase evaporation method. They were characterized by dynamic light scattering (DLS) and transmission electron microscopy (TEM). The results revealed that the DBTP nanovesicles have a spherical structure with an average diameter approximately 138.7nm and a negatively charged surface (-33.3±2.5mV). The loading efficiency of Bex is 76wt% after a simple calculation. In vitro degradation of DBTP nanovesicles and the release of Bex were further studied in detail. The results demonstrated that DBTP nanovesicles were stable in neutral environment but degraded in a weakly acidic condition and released parent drug Bex effectively. Cellular uptake was investigated by confocal laser scanning microscope (CLSM) and liquid chromatography-mass spectroscopy (LC-MS). The results demonstrated the successful internalization and intracellular release of DBTP nanovesicles. Furthermore, the cytotoxicity analysis and apoptosis of the nanovesicles showed higher antitumor activities compared with free Bex. In a conclusion, DBTP nanovesicles could be an effective nanoformulation of Bex.
authors.affiliation: School of Chemistry and Chemical Engineering, Southeast University, Nanjing 210018, China.
authors.forename: Ruiyu
authors.initials: R
authors.lastname: He
authors.affiliation: School of Chemistry and Chemical Engineering, Southeast University, Nanjing 210018, China.
authors.forename: Yawei
authors.initials: Y
authors.lastname: Du
authors.affiliation: School of Chemistry and Chemical Engineering, Southeast University, Nanjing 210018, China.
authors.forename: Longbing
authors.initials: L
authors.lastname: Ling
authors.affiliation: School of Chemistry and Chemical Engineering, Southeast University, Nanjing 210018, China.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Ismail
authors.affiliation: School of Chemistry and Chemical Engineering, Southeast University, Nanjing 210018, China.
authors.forename: Yongpeng
authors.initials: Y
authors.lastname: Hou
authors.affiliation: School of Chemistry and Chemical Engineering, Southeast University, Nanjing 210018, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Yao
authors.affiliation: School of Chemistry and Chemical Engineering, Southeast University, Nanjing 210018, China.. Electronic address: lixs@seu.edu.cn.
authors.forename: Xinsong
authors.initials: X
authors.lastname: Li
mesh_terms: D000072283:A549 Cells; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry*; D017209:Apoptosis / Q000187:drug effects; D000077610:Bexarotene; D002470:Cell Survival / Q000187:drug effects; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry*; D004339:Drug Compounding; D065546:Drug Liberation; D004951:Esterification; D005997:Glycerylphosphorylcholine / Q000737:chemistry*; D006801:Humans; D061986:MCF-7 Cells; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry*; D011355:Prodrugs / Q000008:administration & dosage / Q000737:chemistry*; D013764:Tetrahydronaphthalenes / Q000008:administration & dosage / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D011355:Prodrugs; D013764:Tetrahydronaphthalenes; D005997:Glycerylphosphorylcholine; D000077610:Bexarotene
keywords: Amphiphilic prodrug; Anticancer activity; Bexarotene; Nanovesicles