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聚乳酸-聚乙二醇胶束递送的紫杉醇和拉帕替尼对HER-2阴性乳腺癌细胞的细胞毒性作用

Cytotoxic Effect of Paclitaxel and Lapatinib -Delivered in Polylactide--Poly(ethylene glycol) Micelles on HER-2-Negative Breast Cancer Cells.

作者信息

Zajdel Alicja, Wilczok Adam, Jelonek Katarzyna, Musiał-Kulik Monika, Foryś Aleksander, Li Suming, Kasperczyk Janusz

机构信息

School of Pharmacy with the Division of Laboratory Medicine in Sosnowiec, Medical University of Silesia, Katowice, Poland, Department of Biopharmacy, Jedności 8, 41-200 Sosnowiec, Poland.

Centre of Polymer and Carbon Materials, Polish Academy of Sciences, Curie-Sklodowska 34 St., 41-819 Zabrze, Poland.

出版信息

Pharmaceutics. 2019 Apr 6;11(4):169. doi: 10.3390/pharmaceutics11040169.

DOI:10.3390/pharmaceutics11040169
PMID:30959904
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6523169/
Abstract

To find better strategies to enhance the cytotoxic effect of paclitaxel (PTX) and lapatinib (LAP) against breast cancer cells, we analyzed the efficacy of a novel delivery system containing polylactide-co-poly(ethylene glycol) (PLA-PEG) filomicelles of over 100 nm in length and spherical micelles of approximately 20 nm in diameter. The ¹H NMR measurements confirmed the incorporation of PTX and LAP into micelles. Analysis of the drug release mechanism revealed the diffusion-controlled release of LAP and anomalous transport of PTX. Drug content analysis in lyophilized micelles and micellar solution showed their good storage stability for at least 6 weeks. Blank micelles, LAP-loaded micelles and free LAP did not affect MCF-7 breast cancer cell proliferation, suggesting that the cytotoxicity of PTX-, PTX/LAP-loaded micelles, and the binary mixture of free PTX and LAP was solely caused by PTX. PTX/LAP-loaded micelles showed greater toxicity compared to the binary mixture of PTX and LAP after 48 h and 72 h. Only free PTX alone induced P-gp activity. This study showed the feasibility of using a LAP and PTX combination to overcome MDR in MCF-7 cells, particularly when co-loaded into micelles. We suggest that PTX/LAP micelles can be applicable not only for the therapy of HER-2-positive, but also HER-2-negative breast cancers.

摘要

为了找到更好的策略来增强紫杉醇（PTX）和拉帕替尼（LAP）对乳腺癌细胞的细胞毒性作用，我们分析了一种新型递送系统的疗效，该系统包含长度超过100 nm的聚丙交酯-共-聚（乙二醇）（PLA-PEG）丝状胶束和直径约20 nm的球形胶束。¹H NMR测量证实PTX和LAP已掺入胶束中。药物释放机制分析显示LAP的扩散控制释放和PTX的异常转运。冻干胶束和胶束溶液中的药物含量分析表明它们具有至少6周的良好储存稳定性。空白胶束、载LAP胶束和游离LAP均不影响MCF-7乳腺癌细胞增殖，这表明载PTX、载PTX/LAP胶束以及游离PTX和LAP的二元混合物的细胞毒性完全由PTX引起。48小时和72小时后，载PTX/LAP胶束比PTX和LAP的二元混合物表现出更大的毒性。只有游离PTX单独诱导P-糖蛋白活性。本研究表明使用LAP和PTX联合克服MCF-7细胞中的多药耐药性是可行的，特别是当它们共载于胶束中时。我们建议PTX/LAP胶束不仅可用于治疗HER-2阳性乳腺癌，也可用于治疗HER-2阴性乳腺癌。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ee9f/6523169/eb786006d721/pharmaceutics-11-00169-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ee9f/6523169/6c19017aa251/pharmaceutics-11-00169-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ee9f/6523169/2d5087160c72/pharmaceutics-11-00169-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ee9f/6523169/83fbc38385bb/pharmaceutics-11-00169-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ee9f/6523169/0f11d5c602c6/pharmaceutics-11-00169-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ee9f/6523169/c14b7b99c44e/pharmaceutics-11-00169-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ee9f/6523169/eb786006d721/pharmaceutics-11-00169-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ee9f/6523169/6c19017aa251/pharmaceutics-11-00169-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ee9f/6523169/2d5087160c72/pharmaceutics-11-00169-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ee9f/6523169/83fbc38385bb/pharmaceutics-11-00169-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ee9f/6523169/0f11d5c602c6/pharmaceutics-11-00169-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ee9f/6523169/c14b7b99c44e/pharmaceutics-11-00169-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ee9f/6523169/eb786006d721/pharmaceutics-11-00169-g006.jpg

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