Koziara Joanna M, Whisman Tyler R, Tseng Michael T, Mumper Russell J
Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY 40536-0082, USA.
J Control Release. 2006 May 30;112(3):312-9. doi: 10.1016/j.jconrel.2006.03.001. Epub 2006 Apr 19.
Colloidal carriers have been shown to improve tumor therapy by increased drug delivery into tumor sites resulting directly from the enhanced permeability and retention effect (EPR). However, the clinical outcome of tumor therapy is often limited due to multidrug resistance. Several different types of resistance exist with expression of p-glycoprotein being the most commonly described. Paclitaxel entrapped in emulsifying wax nanoparticles (PX NPs) was shown to overcome drug resistance in a human colon adenocarcinoma cell line (HCT-15). In the present studies, the in-vivo efficacy of PX NPs in a HCT-15 mouse xenograft model was demonstrated. Significant inhibition in tumor growth was observed in mice receiving PX NPs treatment. Additionally, mice dosed with Taxol also demonstrated slower tumor growth; however, the efficacy of the Taxol treatment was shown in the in-vitro HUVEC model to be due to the antiangiogenic effect of paclitaxel. It was concluded that the enhanced efficacy of PX NPs over Taxol in the xenograft model was due to both overcoming paclitaxel resistance and an antiangiogenic effect.
胶体载体已被证明可通过增强的渗透和滞留效应（EPR）直接增加药物向肿瘤部位的递送，从而改善肿瘤治疗。然而，由于多药耐药性，肿瘤治疗的临床结果往往受到限制。存在几种不同类型的耐药性，其中P-糖蛋白的表达是最常被描述的。包裹在乳化蜡纳米颗粒（PX NPs）中的紫杉醇被证明可克服人结肠腺癌细胞系（HCT-15）中的耐药性。在本研究中，证明了PX NPs在HCT-15小鼠异种移植模型中的体内疗效。接受PX NPs治疗的小鼠肿瘤生长受到显著抑制。此外，给予紫杉醇的小鼠肿瘤生长也较慢；然而，紫杉醇治疗的疗效在体外人脐静脉内皮细胞（HUVEC）模型中显示是由于紫杉醇的抗血管生成作用。得出的结论是，在异种移植模型中，PX NPs比紫杉醇具有更高的疗效是由于克服了紫杉醇耐药性和抗血管生成作用。
