title: Topotecan hydrochloride liposomes incorporated into thermosensitive hydrogel for sustained and efficient in situ therapy of H22 tumor in Kunming mice.
abstract: Topotecan hydrochloride (TPT) has potential for the treatment of ovarian cancer, but the activity of TPT tends to decrease due to the ring-opening at physiological pH. In this study, we proposed to incorporate TPT liposomes into injectable thermosensitive in situ hydrogel, consisting of chitosan (CS) and β-glycerophosphate (β-GP), for sustained release and preservation of active lactone form of TPT. The rheology studies were carried out to investigate the sol-gel temperature, flow behavior and viscosity of these CS/β-GP systems. The optimized formulation exhibited sol-gel transition at 40.2 ± 0.4 °C, with pseudoplastic flow behavior. The drug release rate of TPT liposomes loaded CS/β-GP hydrogel in phosphate buffer saline (pH = 7.4) was found to be slowed down, and the lactone fraction of TPT in the hydrogel matrix was maintaining 40% after 50 h. In addition, the antitumor efficacy in Kunming mice bearing Hepatoma-22 tumor, after intratumoral injection of TPT liposomes loaded CS/β-GP hydrogel, was higher than that of TPT in saline and TPT in CS/β-GP hydrogel. Those results demonstrated that TPT liposomes loaded CS/β-GP hydrogel could become a potential formulation for improving the antitumor efficacy of TPT and suggested an important technology platform for intratumoral administration of derivative of camptothecin-family drugs.
authors.affiliation: a Key Laboratory of Modern Chinese Medicines , China Pharmaceutical University , Nanjing , PR China , and.
authors.forename: Jiayu
authors.initials: J
authors.lastname: Xing
authors.affiliation: a Key Laboratory of Modern Chinese Medicines , China Pharmaceutical University , Nanjing , PR China , and.
authors.forename: Xiaole
authors.initials: X
authors.lastname: Qi
authors.affiliation: a Key Laboratory of Modern Chinese Medicines , China Pharmaceutical University , Nanjing , PR China , and.
authors.forename: Yingchun
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: a Key Laboratory of Modern Chinese Medicines , China Pharmaceutical University , Nanjing , PR China , and.
authors.forename: Xuehua
authors.initials: X
authors.lastname: Zhu
authors.affiliation: a Key Laboratory of Modern Chinese Medicines , China Pharmaceutical University , Nanjing , PR China , and.
authors.forename: Ziwei
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: a Key Laboratory of Modern Chinese Medicines , China Pharmaceutical University , Nanjing , PR China , and.
authors.forename: Xiaoxue
authors.initials: X
authors.lastname: Qin
authors.affiliation: a Key Laboratory of Modern Chinese Medicines , China Pharmaceutical University , Nanjing , PR China , and.|b Yangtze River Pharmaceutical Group , State Key Laboratory for Advanced Formulation Technologies , Taizhou , China.
authors.forename: Zhenghong
authors.initials: Z
authors.lastname: Wu
keywords: Chitosan; hydrogels; liposomes; thermosensitivity; topotecan