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Paclitaxel-loaded PLGA microspheres with a novel morphology to facilitate drug delivery and antitumor efficiency

机译：紫杉醇加载的PLGA微球，具有新的形态，可促进药物递送和抗肿瘤效率

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摘要

The aim of this study was to develop a novel morphological paclitaxel (PTX) loaded poly(lactide-co-glycolide) (PLGA) microspheres (MS) delivery system to enhance drug delivery and antitumor efficiency as well as reduce drug administration frequency. Therefore, different morphological types of PTX-PLGA-MS were prepared using a modified solvent evaporation technique. Morphology analysis confirmed the successful preparation of the smooth PTX-PLGA-MS with internal sporadic porosity, and the novel rough PTX-PLGA-MS with microporous surface and porous internal structures. The PTX drugs were distributed in the readily bioavailable state (amorphous) in PTX-loaded MS, which allowed fast drug release from MS following intratumoral administration. The drug entrapment and release behaviors indicated that the rough MS could provide enough hydrophobic space for PTX-loading and deep surface folds for fast matrices degradation, thus achieving a higher drug-loading efficiency (17.8%) and a rapid sustained drug release effect. Furthermore, the rough MS showed strengthened in vitro anti-hepatoma efficiency than that of free PTX and smooth MS. The in vivo studies indicated remarkable antitumor activity of rough MS (tumor inhibition rate = 58.33%) for at least 13 days after a single injection, which was because the rapid sustained-release drugs could induce the pro-apoptosis gene and protein expressions, cause extensive tumor cell apoptosis, and reduce the toxicity to normal tissues. In conclusion, the rough PTX-PLGA-MS drug delivery system with outstanding tumor growth inhibition effect could serve as a promising treatment for liver tumor.
机译：本研究的目的是开发一种新的形态学紫杉醇（PTX）负载的聚（丙交酯 - 共乙酰基）（PLGA）微球（MS）输送系统，以增强药物递送和抗肿瘤效率，以及减少药物给药频率。因此，使用改性溶剂蒸发技术制备不同形态类型的PTX-PLGA-MS。形态学分析证实了具有内部散孔孔隙的光滑PTX-PLGA-MS的成功制备，以及具有微孔表面和多孔内部结构的新型粗糙PTX-PLGA-MS。 PTX药物以PTX负载MS的易于生物可利用的状态（非晶态）分布，其允许从肿瘤内给药后MS的快速释放。药物夹带和释放行为表明，粗糙的MS可以为PTX负载和深表面折叠提供足够的疏水空间，以便快速矩阵降解，从而实现更高的药物负载效率（17.8％）和快速持续的药物释放效果。此外，粗糙的MS显示出比游离PTX和平滑MS的体外抗肝癌效率强化。在一次注射后至少13天的粗mS（肿瘤抑制率= 58.33％）的显着抗肿瘤活性表明了显着的抗肿瘤活性，这是因为快速缓释药物可以诱导促凋亡基因和蛋白质表达，导致广泛的肿瘤细胞凋亡，并降低正常组织的毒性。总之，具有出色的肿瘤生长抑制作用的粗糙PTX-PLGA-MS药物递送系统可以作为肝肿瘤的有希望的处理。

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  • 来源
    《RSC Advances》 |2018年第6期|共12页
  • 作者

    Zhang Zongrui; Wang Xinyu; Li Binbin; Hou Yuanjing; Cai Zhengwei; Yang Jing; Li Yi;

  • 作者单位

    Wuhan Univ Technol State Key Lab Adv Technol Mat Synth &

    Proc Wuhan 430070 Hubei Peoples R China;

    Wuhan Univ Technol State Key Lab Adv Technol Mat Synth &

    Proc Wuhan 430070 Hubei Peoples R China;

    Wuhan Univ Technol State Key Lab Adv Technol Mat Synth &

    Proc Wuhan 430070 Hubei Peoples R China;

    Wuhan Univ Technol State Key Lab Adv Technol Mat Synth &

    Proc Wuhan 430070 Hubei Peoples R China;

    Wuhan Univ Technol State Key Lab Adv Technol Mat Synth &

    Proc Wuhan 430070 Hubei Peoples R China;

    Wuhan Univ Technol Sch Foreign Languages Wuhan 430070 Hubei Peoples R China;

    Hong Kong Polytech Univ Inst Text &

    Clothing Kowloon Hong Kong Peoples R China;

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