title: Sustained release of PTX-incorporated nanoparticles synergized by burst release of DOX⋅HCl from thermosensitive modified PEG/PCL hydrogel to improve anti-tumor efficiency.
abstract: As drug therapies become increasingly sophisticated, the synergistic benefits of two or more drugs are often required. In this study, we aimed at improving anti-tumor efficiency of paclitaxel (PTX)-incorporated thermo-sensitive injectable hydrogel by the synergy of burst release of doxorubicin hydrochloride (DOX⋅HCl). Thermosensitive injectable hydrogel composed of nanoparticles assembled from amphiphilic copolymer poly(ε-caprolactone-co-1,4,8-trioxa[4.6]spiro-9-undecanone)-poly(ethylene glycol)-poly(ε-caprolaone-co-1,4,8-trioxa[4.6]spiro-9-undecanone) (PECT) was fabricated. Hydrophobic PTX and hydrophilic DOX⋅HCl were loaded simultaneously in the thermo-sensitive injectable hydrogel by a two-stage entrapment. Thermosensitive gelling behaviors of drug-loading PECT nanoparticle aqueous dispersions were studied. In vitro release profiles of PTX and DOX⋅HCl and in vivo anti-tumor effect by dual drugs from PECT hydrogel were investigated. The results showed that hydrophilic and hydrophobic drugs could be successfully entrapped in PECT hydrogel simultaneously without affecting its thermo-sensitive behavior. In vitro release profiles demonstrated the burst release of DOX⋅HCl and the sustained release of PTX. Anti-tumor effect was improved by a fast and tense attack caused by the burst release of hydrophilic DOX⋅HCl from hydrogel, which was continued by the sequent sustained release of PTX-incorporated nanoparticles and remnant DOX⋅HCl. Unintentionally, entrapped in PECT hydrogel, hydrophilic DOX⋅HCl was observed to have a sustained releasing pattern in vitro and in vivo.
authors.affiliation: Department of Polymer Science and Technology, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, China.
authors.forename: Shuxin
authors.initials: S
authors.lastname: Xu
authors.affiliation: Institute of Biomedical Engineering, Chinese Academy of Medical Science, Tianjin 300072, China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Tianjin Institute of Medical and Pharmaceutical Science, Tianjin 300020, China.
authors.forename: Xijing
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Polymer Science and Technology, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, China.
authors.forename: Jianping
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Polymer Science and Technology, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, China; Key Laboratory of Systems Bioengineering of the Ministry of Education, Tianjin 300072, China; Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin 300072, China.
authors.forename: Anjie
authors.initials: A
authors.lastname: Dong
authors.affiliation: Department of Polymer Science and Technology, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, China. Electronic address: dengliandong@tju.edu.cn.
authors.forename: Liandong
authors.initials: L
authors.lastname: Deng
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry; D002286:Carcinoma, Ehrlich Tumor / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000737:chemistry; D004317:Doxorubicin / Q000008:administration & dosage / Q000737:chemistry; D004337:Drug Carriers / Q000008:administration & dosage* / Q000737:chemistry; D065546:Drug Liberation; D020100:Hydrogels / Q000737:chemistry; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry; D017239:Paclitaxel / Q000008:administration & dosage / Q000737:chemistry; D011091:Polyesters / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D013696:Temperature; D047368:Tumor Burden / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D020100:Hydrogels; D011091:Polyesters; C016240:polycaprolactone; D011092:Polyethylene Glycols; D004317:Doxorubicin; D017239:Paclitaxel
keywords: Anti-tumor; Doxorubicin hydrochloride (PubChem CID: 443939); Dual drugs; Ethylene glycol (PubChem CID: 174); Hydrogel; Nanoparticle; Paclitaxel (PubChem CID: 36314); Synergy; Thermo-sensitive; ε-Caprolactone (PubChem CID: 10401)