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  • Title: A reconstituted thermosensitive hydrogel system based on paclitaxel-loaded amphiphilic copolymer nanoparticles and antitumor efficacy.
    Author: Liang Y, Dong C, Zhang J, Deng L, Dong A.
    Journal: Drug Dev Ind Pharm; 2017 Jun; 43(6):972-979. PubMed ID: 28121206.
    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/PEOALAGel based on paclitaxel (PTX)-loaded PEOALA nanoparticles (NPs). PTX/PEOALAGel could 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/PEOALAGel showed 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/PEOALAGel formulation 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/PEOALAGel could 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/PEOALAGel combination local delivery system could enhance tumor inhibition effect and tumor accumulation of PTX, and lower the systemic exposure. So, the reconstituted PTX/PEOALAGel system could potentially be a useful vehicle for regional cancer chemotherapy.
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