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可注射阿霉素表面修饰纤维素纳米纤维凝胶的制备及其对黑色素瘤的抗肿瘤和抗转移活性评估

Preparation of an injectable doxorubicin surface modified cellulose nanofiber gel and evaluation of its anti-tumor and anti-metastasis activity in melanoma.

作者信息

Alizadeh Najmeh, Akbari Vajihe, Nurani Maryam, Taheri Azade

机构信息

Dept. of Pharmaceutics, Novel Drug Delivery Systems Research Center, Faculty of Pharmacy, Isfahan University of Medical sciences, Isfahan, Iran.

Dept. of Pharmaceutical Biotechnology and Isfahan Pharmaceutical Research Center, Faculty of Pharmacy, Isfahan University of Medical Sciences, Isfahan, Iran.

出版信息

Biotechnol Prog. 2018 Mar;34(2):537-545. doi: 10.1002/btpr.2598. Epub 2018 Jan 17.

DOI:10.1002/btpr.2598
PMID:29314760
Abstract

Cellulose nanofibers (Cel-NFs) gel can be considered as a useful drug carrier because of its biocompatibility, high specific surface area, and high loading capacity of drugs. Injectable Cel-NFs gel could deliver doxorubicin (DOX) for localized chemotherapy of melanoma and suppress melanoma cells migration because of the physical barrier property of Cel-NFs. We prepared DOX surface modified Cel-NFs (DOX-Cel-NFs) gel by the electrostatic attachment of DOX molecules on the surface of Cel-NFs. The increase in the zeta potential of nanofibers and the changes in the FTIR spectra of DOX-Cel-NFs compared to Cel-NFs proved this attachment. DOX-Cel-NFs showed nano-fibrous structure with an average diameter of 22.32 ± 10.66 nm after analyzing using field emission scanning electron microscopy. The suitable injectability of DOX-Cel-NFs gel verified its promising application for the localized chemotherapy. DOX-Cel-NFs gel exhibited a sustained drug release manner. The cytotoxicity results showed that DOX-Cel-NFs were more cytotoxic against melanoma cancer cells than the free DOX during 48 h incubation period. Moreover, DOX-Cel-NFs gel can suppress the melanoma cancer cells migration efficiently. Thus our results emphasize the potential of DOX-Cel-NFs gel as a chemotherapeutic agent for local delivery of DOX in order to treat melanoma and prevent its metastasis. © 2018 American Institute of Chemical Engineers Biotechnol. Prog., 34:537-545, 2018.

摘要

纤维素纳米纤维(Cel-NFs)凝胶因其生物相容性、高比表面积和高药物负载能力,可被视为一种有用的药物载体。可注射的Cel-NFs凝胶能够递送阿霉素(DOX)用于黑色素瘤的局部化疗,并且由于Cel-NFs的物理屏障特性可抑制黑色素瘤细胞迁移。我们通过将DOX分子静电附着在Cel-NFs表面制备了DOX表面修饰的Cel-NFs(DOX-Cel-NFs)凝胶。与Cel-NFs相比,纳米纤维的zeta电位增加以及DOX-Cel-NFs的FTIR光谱变化证明了这种附着。使用场发射扫描电子显微镜分析后,DOX-Cel-NFs呈现出平均直径为22.32±10.66 nm的纳米纤维结构。DOX-Cel-NFs凝胶合适的可注射性证实了其在局部化疗方面的应用前景。DOX-Cel-NFs凝胶呈现出药物持续释放的方式。细胞毒性结果表明,在48小时的孵育期内,DOX-Cel-NFs对黑色素瘤癌细胞的细胞毒性比游离DOX更强。此外,DOX-Cel-NFs凝胶能够有效抑制黑色素瘤癌细胞迁移。因此,我们的结果强调了DOX-Cel-NFs凝胶作为一种化疗剂用于局部递送DOX以治疗黑色素瘤并防止其转移的潜力。© 2018美国化学工程师学会生物技术进展,34:537 - 545,2018。

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