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一种新型可尺寸调节的纳米载体系统,用于靶向抗癌药物递送。

A novel size-tunable nanocarrier system for targeted anticancer drug delivery.

机构信息

Division of Hematology & Oncology, Department of Internal Medicine, UCD Cancer Center, University of California Davis, Sacramento, CA 95817, USA.

出版信息

J Control Release. 2010 Jun 15;144(3):314-23. doi: 10.1016/j.jconrel.2010.02.027. Epub 2010 Mar 6.


DOI:10.1016/j.jconrel.2010.02.027
PMID:20211210
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2878919/
Abstract

We have developed a nanocarrier drug-delivery system based on micelles formed by a new class of well-defined linear PEGylated two-arm oligomer of cholic acids in aqueous solution. By varying the length of the linear PEG chains and the configuration of cholic acid oligomer, one can easily fine-tune the physicochemical properties of the amphiphilic polymers and the resulting micelles. These include particle size, critical micelle concentration, and drug-loading capacity. High level of hydrophobic anticancer drugs such as PTX, etoposide and SN-38 can be readily loaded into such nanocarriers. The loading capacity of the nanocarrier for PTX (PTX) is extremely high (12.0mg/mL), which is equivalent to 37.5% (w/w) of the total mass of the micelle. PTX-loaded nanocarriers are much more stable than Abraxane (PTX/human serum albumin nanoaggregate) when stored in bovine serum albumin solution or dog plasma. PTX release profile from the micelles is burst-free and sustained over a period of seven days. The anti-tumor activity of PTX-loaded nanocarriers against ovarian cancer cell line in vitro, with continuous drug exposure, is similar to Taxol (formulation of PTX dissolved in Cremophor EL and ethanol) or Abraxane. Targeted drug delivery to tumor site with these novel micelles was demonstrated by near infrared fluorescence (NIRF) imaging in nude mice bearing ovarian cancer xenograft. Furthermore, PTX-loaded nanocarriers demonstrated superior anti-tumor efficacy compared to Taxol at equivalent PTX dose in ovarian cancer xenograft model.

摘要

我们开发了一种基于胶束的纳米载体药物传递系统,该胶束由新型的、结构明确的、在水溶液中形成的两亲性线性聚乙二醇化胆酸两臂寡聚物形成。通过改变线性聚乙二醇链的长度和胆酸寡聚物的构型,可以轻松地调整两亲聚合物和所得胶束的物理化学性质。这些性质包括粒径、临界胶束浓度和载药能力。可以很容易地将高疏水性抗癌药物如紫杉醇、依托泊苷和 SN-38 载入这种纳米载体中。该纳米载体对紫杉醇(PTX)的载药能力极高(12.0mg/mL),相当于胶束总质量的 37.5%(w/w)。与 Abraxane(载紫杉醇的人血清白蛋白纳米颗粒)相比,载药纳米载体在牛血清白蛋白溶液或狗血浆中储存时更加稳定。载药胶束的紫杉醇释放曲线无突释且持续七天。紫杉醇负载纳米载体在体外对卵巢癌细胞系的抗肿瘤活性,随着药物的持续暴露,与紫杉醇(溶于聚氧乙烯蓖麻油和乙醇中的紫杉醇制剂)或 Abraxane 相似。通过携带卵巢癌异种移植的裸鼠近红外荧光(NIRF)成像,证明了这些新型胶束对肿瘤部位的靶向药物递送。此外,与 Taxol 相比,在卵巢癌异种移植模型中,载紫杉醇纳米载体在等效的 PTX 剂量下表现出更好的抗肿瘤疗效。

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本文引用的文献

[1]
A self-assembling nanoparticle for paclitaxel delivery in ovarian cancer.

Biomaterials. 2009-10

[2]
Targeted nanoassembly loaded with docetaxel improves intracellular drug delivery and efficacy in murine breast cancer model.

Mol Pharm. 2008

[3]
Novel thermo-sensitive core-shell nanoparticles for targeted paclitaxel delivery.

Nanotechnology. 2009-2-11

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Int J Pharm. 2009-7-6

[5]
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Bioconjug Chem. 2009-1

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Bioconjug Chem. 2009-2

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Nat Nanotechnol. 2008-3

[8]
Stability issues of polymeric micelles.

J Control Release. 2008-10-6

[9]
Synthesis and characterization of star poly(epsilon-caprolactone)-b-poly(ethylene glycol) and poly(L-lactide)-b-poly(ethylene glycol) copolymers: evaluation as drug delivery carriers.

Bioconjug Chem. 2008-7

[10]
Release of hydrophobic molecules from polymer micelles into cell membranes revealed by Forster resonance energy transfer imaging.

Proc Natl Acad Sci U S A. 2008-5-6

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