PHB-Based Gels as Delivery Agents of Chemotherapeutics for the Effective Shrinkage of Tumors.
Injectable thermogel to deliver chemotherapeutics in a minimally invasive manner and to achieve their long term sustained release at tumor sites to minimize side effects is attractive for chemotherapy and precision medicine, but its rational design remains a challenge. In this work, a copolymer with natural biodegradable poly[(R)-3-hydroxybutyrate] (PHB), hydrophilic poly(ethylene glycol), and temperature sensitive poly(propylene glycol) blocks linked by urethane linkages is designed to show thermogelling characteristics which are beneficial for minimally invasive injection and safe degradation. This thermogelling polymer possesses in vitro biocompatibility with very low cyto-toxicity in HEK293 cells. Furthermore, it is able to form the gel to achieve the controllable release of paclitaxel (PTX) and doxorubicin (DOX) by adjusting polymer concentrations. A rodent model of hepatocarcinoma has been performed to demonstrate the in vivo applications of this PHB-based thermogel. The drug-loaded thermogel has been intratumorally injected and both PTX-loaded and DOX-loaded thermogel have significantly slowed down tumor growth. This work represents the first time that injectable PHB thermogels have possessed good controllable release effect of chemotherapeutics against the in vivo model of tumors and will benefit various applications, including on-demand drug delivery and personalized medicine.
School of Pharmaceutical Sciences, Xiamen University, Xiamen, 361102, P. R. China. wuyl@xmu.edu.cn.
Yun-Long
YL
Wu
School of Pharmaceutical Sciences, Xiamen University, Xiamen, 361102, P. R. China.
Han
H
Wang
School of Pharmaceutical Sciences, Xiamen University, Xiamen, 361102, P. R. China.
Ying-Kun
YK
Qiu
Institute of Materials Research and Engineering, A*STAR (Agency for Science, Technology and Research), 2 Fusionopolis Way, Innovis, #08-03, Singapore, 138634, Singapore.
Sing Shy
SS
Liow
Institute of Materials Research and Engineering, A*STAR (Agency for Science, Technology and Research), 2 Fusionopolis Way, Innovis, #08-03, Singapore, 138634, Singapore.
Zibiao
Z
Li
Institute of Materials Research and Engineering, A*STAR (Agency for Science, Technology and Research), 2 Fusionopolis Way, Innovis, #08-03, Singapore, 138634, Singapore. lohxj@imre.a-star.edu.sg.|Department of Materials Science and Engineering, National University of Singapore, 9 Engineering Drive 1, Singapore, 117576, Singapore. lohxj@imre.a-star.edu.sg.|Singapore Eye Research Institute, 11 Third Hospital Avenue, Singapore, 168751, Singapore. lohxj@imre.a-star.edu.sg.
Xian Jun
XJ
Loh
D020155:3-Hydroxybutyric Acid / Q000008:administration & dosage / Q000737:chemistry*; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry*; D002460:Cell Line; D004317:Doxorubicin / Q000008:administration & dosage / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods; D005260:Female; D005782:Gels / Q000008:administration & dosage* / Q000737:chemistry*; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009369:Neoplasms / Q000188:drug therapy*; D017239:Paclitaxel / Q000008:administration & dosage / Q000737:chemistry; D011091:Polyesters / Q000008:administration & dosage / Q000737:chemistry; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000737:chemistry; D011108:Polymers / Q000737:chemistry; D000091402:Prohibitins; D013696:Temperature
D000970:Antineoplastic Agents; D004337:Drug Carriers; D005782:Gels; C000717328:PHB protein, human; D011091:Polyesters; D011108:Polymers; D000091402:Prohibitins; D011092:Polyethylene Glycols; D004317:Doxorubicin; D017239:Paclitaxel; D020155:3-Hydroxybutyric Acid
drug delivery; poly([R]-hydroxybutyrate); thermogelling; transesterification