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In vivo evaluation of novel pH-sensitive mPEG-Hz-chol conjugate in liposomes: Pharmacokinetics, tissue distribution, efficacy assessment

机译:脂质体中新型pH敏感的mPEG-Hz-chol偶联物的体内评估:药代动力学,组织分布,功效评估

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摘要

As is known, paclitaxel (PTX), one of the most effective anticancer drugs on the market today, has been demonstrated in clinical trials against a wide variety of tumors, including ovarian carcinoma, breast cancer, head and neck cancers, and non-small cell lung cancer [1-4]. However, its low aqueous solubility is one of the biggest shortcomings of PTX. The current clinical dosage form of PTX is dissolved in a mixture of Cremophor? EL (poly-oxyethylated caster oil) and ethanol (50:50, v/v) and needs to be diluted before injection. However, Cremophor? EL has been associated with serious side-effects and leads to hypersensitivity, nephrotoxicity, and neurotoxicity in many patients [3]. In order to increase the therapeutic efficiency and reduce the side-effects caused by these vehicles, much effort has been devoted to improving the aqueous solubility of PTX without using Cremophor? EL [5].
机译:众所周知,紫杉醇(PTX)是当今市场上最有效的抗癌药物之一,已在针对多种肿瘤的临床试验中得到证实,包括卵巢癌,乳腺癌,头颈癌和非小细胞肺癌。细胞肺癌[1-4]。但是,其低的水溶性是PTX的最大缺点之一。当前的PTX临床剂型溶解在Cremophor?的混合物中。 EL(聚氧乙烯蓖麻油)和乙醇(50:50,v / v),需要在注射前稀释。但是,Cremophor? EL已与严重的副作用相关,并导致许多患者出现超敏反应,肾毒性和神经毒性[3]。为了提高治疗效率并减少由这些媒介物引起的副作用,已经在不使用CremophorTM的情况下投入了很多努力来改善PTX的水溶性。 EL [5]。

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