title: A reconstituted thermosensitive hydrogel system based on paclitaxel-loaded amphiphilic copolymer nanoparticles and antitumor efficacy.
abstract: Combination delivery systems composed of injectable hydrogels and drug-incorporated nanoparticles are urgently in regional cancer chemotherapy to facilitate efficient delivery of chemotherapeutic agents, enhance antitumor efficiency, and decrease side effects. Here, we developed a novel thermosensitive amphiphilic triblock copolymer consisting of methoxy poly(ethylene glycol), poly(octadecanedioic anhydride), and d,l-lactic acid oligomer (PEOALA), built a combination system of thermosensitive injectable hydrogel PTX/PEOALAGelbased on paclitaxel (PTX)-loaded PEOALA nanoparticles (NPs). PTX/PEOALAGelcould be stored as freeze-dried powders of paclitaxel-loaded PEOALA NPs, which could be easily redispersed into the water at ambient temperature, and form a hydrogel at the injected site in vivo. The in vitro cytotoxicity of PTX/PEOALAGelshowed no obvious cytotoxicity in comparison with Taxol® against MCF-7 and HeLa cells. However, the in vivo antitumor activity showed that a single intratumoral injection of the PTX/PEOALAGelformulation was more effective than four intravenous (i.v.) injections of Taxol®at a total dosage of 20 mg/kg in inhibiting the growth of MCF-7 tumor-bearing Balb/c mice, and the inhibition could be sustained for more than 17 d. The pharmacokinetic study demonstrated that the intratumoral injection of PTX/PEOALAGelcould greatly decrease the systemic exposure of PTX, as confirmed by the rather low plasma concentration, and prolonged circulation time and enhanced tumor PTX accumulation, implying fewer off-target side effects. In summary, the PTX/PEOALAGelcombination local delivery system could enhance tumor inhibition effect and tumor accumulation of PTX, and lower the systemic exposure. So, the reconstituted PTX/PEOALAGelsystem could potentially be a useful vehicle for regional cancer chemotherapy.
authors.affiliation: a State Key Laboratory of Natural and Biomimetic Drugs , School of Pharmaceutical Sciences, Peking University , Beijing , China.
authors.forename: Yanqin
authors.initials: Y
authors.lastname: Liang
authors.affiliation: b Department of Laboratory , People's Hospital of Jiyang County , Shandong , China.
authors.forename: Chengxia
authors.initials: C
authors.lastname: Dong
authors.affiliation: c Department of Polymer Science and Technology , School of Chemical Engineering and Technology, Tianjin University , Tianjin , China.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Zhang
authors.affiliation: c Department of Polymer Science and Technology , School of Chemical Engineering and Technology, Tianjin University , Tianjin , China.
authors.forename: Liandong
authors.initials: L
authors.lastname: Deng
authors.affiliation: c Department of Polymer Science and Technology , School of Chemical Engineering and Technology, Tianjin University , Tianjin , China.
authors.forename: Anjie
authors.initials: A
authors.lastname: Dong
mesh_terms: D061605:Administration, Intravenous; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000494:pharmacology* / Q000627:therapeutic use; D004339:Drug Compounding; D004354:Drug Screening Assays, Antitumor; D005260:Female; D005612:Freeze Drying; D006367:HeLa Cells; D006801:Humans; D020100:Hydrogels; D061986:MCF-7 Cells; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles; D017239:Paclitaxel / Q000008:administration & dosage* / Q000494:pharmacology* / Q000627:therapeutic use; D011108:Polymers; D014018:Tissue Distribution; D023041:Xenograft Model Antitumor Assays
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D020100:Hydrogels; D011108:Polymers; D017239:Paclitaxel
keywords: Reconstituted thermosensitive hydrogel; amphiphilic copolymer; local chemotherapy; nanoparticles; paclitaxel