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Tytuł:
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A reconstituted “two into one” thermosensitive hydrogel system assembled by drug-loaded amphiphilic copolymer nanoparticles for the local delivery of paclitaxelElectronic supplementary information (ESI) available. See DOI: 10.1039/c2tb00068g
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Autorzy:
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Wang, Weiwei
Deng, Liandong
Xu, Shuxin
Zhao, Xiumei
Lv, Nan
Zhang, Guixian
Gu, Na
Hu, Renjie
Zhang, Jianhua
Liu, Jinjian
Dong, Anjie
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Źródło:
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Journal of Materials Chemistry B; 2012, Vol. 1 Issue: 4 p552-563, 12p
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Combination delivery systems composed of injectable hydrogels and drug-incorporated micelles or nanoparticles with tunable and convenient properties for clinical operation and storage are urgently demanded in regional cancer chemotherapy to prolong and control drug release, enhance antitumor efficiency and decrease side effects. Previously, we developed a novel thermosensitive amphiphilic triblock copolymer, poly(-caprolactone-co-1,4,8-trioxa[4.6]spiro-9-undecanone)–poly(ethylene glycol)–poly(-caprolactone-co-1,4,8-trioxa[4.6]spiro-9-undecanone) (PECT), and fabricated a reconstituted “two into one” combination system of thermosensitive injectable hydrogel PTX/PECTGel, assembled from paclitaxel (PTX)-loaded PECT nanoparticles (NPs). PTX/PECTGelcould be stored as freeze-dried powders of paclitaxel-loaded PECT NPs, which could be reconstituted into aqueous fluid dispersions at ambient temperature just by mixing with water after gentle stirring for several minutes, and form a hydrogel at the injected site in vivo. Herein, the drug release, in vivomorphology, antitumor efficiency and pharmacokinetic properties of PTX/PECTGelwere evaluated. The PTX/PECTGelcombination system could continuously release PTX in a near linear manner over 42 days in vitro, and simultaneously, PTX/PECT NPs containing 75% of the total released PTX could dissociate from the PTX/PECTGel. PTX/PECTGelexhibited remarkable in vitroanti-proliferative activities against Ehrlich ascites carcinoma (EAC) cancer cells. The peritumorally or intratumorally injected PECT gel could cover the entire surface or fill up the interior space of the tumor, respectively. A single peritumoral injection of the PTX/PECTGelformulation at a low dosage of 10 mg kg−1could completely inhibit the growth of an EAC tumor inoculated in Balb/c mice after the first week, and the inhibition could be sustained for more than 21 days. The plasma pharmacokinetic study demonstrated that PTX/PECTGelcould greatly decrease the systemic exposure of PTX, as confirmed by the rather low plasma concentration. On the other hand, the PTX concentration in normal tissues with the intratumoral injection of PTX/PECTGelwas approximately 2 μg g−1, which was 3–10 times lower than that with the intraperitoneal or intratumoral injection of Taxol®, implying fewer off-target side effects. These data confirmed that the PTX/PECTGelcombination local delivery system could vastly prolong the in vitroand in vivopaclitaxel release, enhance the local tumor inhibition effect and lower the systemic exposure and tissue distribution of paclitaxel. Hence, the “two into one” PTX/PECTGelsystem holds underlying value for regional cancer chemotherapy.