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首页> 外文期刊>Biomaterials Science >Paclitaxel-loaded pH responsive hydrogel based on self-assembled peptides for tumor targeting
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Paclitaxel-loaded pH responsive hydrogel based on self-assembled peptides for tumor targeting

机译：紫杉醇加载的pH响应水凝胶基于自组装肽的肿瘤靶向

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摘要

Intratumoral delivery of chemotherapeutic agents may permit the localization of drugs in tumors, decrease nonspecific targeting and increase efficacy. The pH-responsive peptide hydrogel is considered a suitable carrier for chemotherapeutics via intratumoral injection. Thus, a study was carried out to develop a paclitaxel (PTX) drug delivery system using a pH-responsive FER-8 peptide hydrogel for tumor targeting. The pH-sensitive hydrogel system was characterized for loading capacity, acid sensitivity, structure, rheology, morphology, drug release, in vitro cytotoxicity and in vivo efficacy in H22 tumor-bearing mice. The stable FER-8 peptide hydrogel with high drug-loading capacity was formed at pH 7.4 by the self-assembly of peptide, whereas higher degradation was observed at an acidic pH. Circular dichroism and rheology confirmed the suitable meshwork structure and enhanced mechanical properties of the hydrogel. The FER-8 peptide hydrogel fibers were found to have an average size less than 500 nm at pH 7.4, which was confirmed by TEM and DLS analysis. Sustained release of PTX at pH 5.5 was observed for the FER-8 peptide hydrogel (HG-PTX) for almost 1 week. In vitro cytotoxicity studies indicated that the FER-8 peptide hydrogel increased the drug accumulation in HepG2 cells and effectively inhibited the growth of HepG2 tumor cells compared with free drugs. Furthermore, in vivo studies using H22-bearing mice indicated that the paclitaxel-loaded FER-8 peptide hydrogel significantly increased the amount of drugs in tumor tissues and showed prolonged retention (96 hours) at the tumor site by intratumoral injection. The in vivo anti-tumor studies confirmed the pH-sensitive properties of HG-PTX, which allowed the drug to be triggered by the acidic pH environment at tumor sites, provided sustained delivery of the drug and enhanced tumor inhibition. In conclusion, HG-PTX provides an attractive strategy and potential vehicle for efficient anti-cancer drug delivery. The carrier can enhance tumor targeting, prolong retention, reduce systemic side effects and increase the accumulation of drugs at the tumor site.
机译：化学治疗剂的妥善递送可以允许肿瘤中的药物定位，降低非特异性靶向并增加疗效。 pH-响应肽水凝胶通过腹腔内注射被认为是化学治疗剂的合适载体。因此，进行了一种使用pH响应FER-8肽水凝胶进行紫杉醇（PTX）药物递送系统，用于肿瘤靶向。 pH敏感水凝胶系统的特征在于加载能力，酸敏感性，结构，流变学，形态学，药物释放，体外细胞毒性，以及在H22携带的小鼠中的体内疗效。通过肽的自组装在pH7.4处形成具有高药物负载能力的稳定FER-8肽水凝胶，而在酸性pH下观察到更高的降解。圆形二色性和流变学证实了合适的网状结构和水凝胶的增强力学性能。发现FER-8肽水凝胶纤维在pH 7.4下具有小于500nm的平均尺寸，其通过TEM和DLS分析证实。对于FER-8肽水凝胶（HG-PTX），观察到pH5.5在pH5.5的持续释放近1周。体外细胞毒性研究表明，FER-8肽水凝胶增加了HepG2细胞中的药物积累，并有效地抑制了与游离药物相比的HepG2肿瘤细胞的生长。此外，使用H22轴承小鼠的体内研究表明，紫杉醇负载的FER-8肽水凝胶显着增加了肿瘤组织中的药物量，并通过妥善注射显示肿瘤部位的延长保留（96小时）。体内抗肿瘤研究证实了HG-PTX的pH敏感性，其使药物允许通过肿瘤部位的酸性pH环境引发，提供药物的持续递送和增强的肿瘤抑制。总之，HG-PTX提供了有吸引力的抗癌药物递送的策略和潜在的载体。载体可以增强肿瘤靶向，延长保留，降低全身副作用并增加肿瘤部位的药物的积累。

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  • 来源
    《Biomaterials Science》 |2019年第5期|共14页
  • 作者

    Raza Faisal; Zhu Ying; Chen Li; You Xinru; Zhang Jiayuan; Khan Asifullah; Khan Muhammad Waseem; Hasnat Muhammad; Zafar Hajra; Wu Jun; Ge Liang;

  • 作者单位

    China Pharmaceut Univ State Key Lab Nat Med 24 Tongjia Xiang Nanjing 210009 Jiangsu Peoples R China;

    China Pharmaceut Univ State Key Lab Nat Med 24 Tongjia Xiang Nanjing 210009 Jiangsu Peoples R China;

    Xinjiang Med Univ Sch Pharm 393 Xinyi Rd Urumqi 830054 Xinjiang Peoples R China;

    Sun Yat Sen Univ Sch Biomed Engn Guangzhou 510006 Guangdong Peoples R China;

    True Light Middle Sch Guangzhou Guangzhou 510380 Guangdong Peoples R China;

    China Pharmaceut Univ State Key Lab Nat Med 24 Tongjia Xiang Nanjing 210009 Jiangsu Peoples R China;

    Huazhong Univ Sci &

    Technol Sch Pharm Tongji Med Coll Wuhan 430030 Hubei Peoples R China;

    China Pharmaceut Univ State Key Lab Nat Med 24 Tongjia Xiang Nanjing 210009 Jiangsu Peoples R China;

    Quaid I Azam Univ Dept Pharm Islamabad 45320 Pakistan;

    Sun Yat Sen Univ Sch Biomed Engn Guangzhou 510006 Guangdong Peoples R China;

    China Pharmaceut Univ State Key Lab Nat Med 24 Tongjia Xiang Nanjing 210009 Jiangsu Peoples R China;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 分子生物学;
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