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多柔比星负载泊洛沙姆温敏水凝胶的化学、药理学和生物学评价。

Doxorubicin Loaded Poloxamer Thermosensitive Hydrogels: Chemical, Pharmacological and Biological Evaluation.

机构信息

Department of Radiology, division Translational Nanobiomaterials and Imaging, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands.

JeNaCell GmbH, Winzerlaer Straße 2, 07745 Jena, Germany.

出版信息

Molecules. 2020 May 8;25(9):2219. doi: 10.3390/molecules25092219.

DOI:10.3390/molecules25092219
PMID:32397328
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7248767/
Abstract

(1) Background: doxorubicin is a potent chemotherapeutic agent, but it has limitations regarding its side effects and therapy resistance. Hydrogels potentially deal with these problems, but several characterizations need to be optimized to better understand how hydrogel assisted chemotherapy works. Poloxamer 407 (P407) hydrogels were mixed with doxorubicin and physico-chemical, biological, and pharmacological characterizations were considered. (2) Methods: hydrogels were prepared by mixing P407 in PBS at 4 °C. Doxorubicin was added upon solutions became clear. Time-to-gelation, hydrogel morphology, and micelles were studied first. The effects of P407-doxorubicin were evaluated on MC-38 colon cancer cells. Furthermore, doxorubicin release was assessed and contrasted with non-invasive in vivo whole body fluorescence imaging. (3) Results: 25% P407 had favorable gelation properties with pore sizes of 30-180 µm. P407 micelles were approximately 5 nm in size. Doxorubicin was fully released in vitro from 25% P407 hydrogel within 120 h. Furthermore, P407 micelles strongly enhanced the anti-neoplastic effects of doxorubicin on MC-38 cells. In vivo fluorescence imaging revealed that hydrogels retained fluorescence signals at the injection site for 168 h. (4) Conclusions: non-invasive imaging showed how P407 gels retained drug at the injection site. Doxorubicin P407 micelles strongly enhanced the anti-tumor effects.

摘要

(1)背景:阿霉素是一种有效的化疗药物,但它在副作用和耐药性方面存在局限性。水凝胶可能可以解决这些问题,但需要对几种特性进行优化,以更好地理解水凝胶辅助化疗的作用。本文将泊洛沙姆 407(P407)水凝胶与阿霉素混合,并对其物理化学、生物学和药理学特性进行了研究。(2)方法:将 P407 在 PBS 中于 4°C 下混合制成水凝胶。溶液澄清后加入阿霉素。首先研究了水凝胶的胶凝时间、水凝胶形态和胶束。评估了 P407-阿霉素对 MC-38 结肠癌细胞的影响。此外,还评估了阿霉素的释放情况,并与非侵入性体内全身荧光成像进行了对比。(3)结果:25%的 P407 具有良好的胶凝性能,孔径为 30-180µm。P407 胶束的直径约为 5nm。25%的 P407 水凝胶在 120 小时内可完全释放阿霉素。此外,P407 胶束可显著增强阿霉素对 MC-38 细胞的抗肿瘤作用。体内荧光成像显示,水凝胶在注射部位保留荧光信号长达 168 小时。(4)结论:非侵入性成像显示了 P407 凝胶如何将药物保留在注射部位。阿霉素 P407 胶束可显著增强抗肿瘤作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb30/7248767/a3df63c36080/molecules-25-02219-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb30/7248767/f7e6a51ed1ef/molecules-25-02219-g0A1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb30/7248767/b664416e1e93/molecules-25-02219-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb30/7248767/c4422c25cd03/molecules-25-02219-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb30/7248767/9ff023bfc020/molecules-25-02219-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb30/7248767/66f5b971b032/molecules-25-02219-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb30/7248767/a3a049be21a1/molecules-25-02219-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb30/7248767/a3df63c36080/molecules-25-02219-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb30/7248767/f7e6a51ed1ef/molecules-25-02219-g0A1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb30/7248767/b664416e1e93/molecules-25-02219-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb30/7248767/c4422c25cd03/molecules-25-02219-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb30/7248767/9ff023bfc020/molecules-25-02219-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb30/7248767/66f5b971b032/molecules-25-02219-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb30/7248767/a3a049be21a1/molecules-25-02219-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb30/7248767/a3df63c36080/molecules-25-02219-g006.jpg

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