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首页> 外文期刊>RSC Advances >In situ gel-forming dual drug delivery system for synergistic combination therapy of colorectal peritoneal carcinomatosis
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In situ gel-forming dual drug delivery system for synergistic combination therapy of colorectal peritoneal carcinomatosis

机译：原位凝胶形成双药物递送系统，具有结肠直肠腹膜癌变病的协同组合治疗

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摘要

Colorectal peritoneal carcinomatosis (CRPC) is a common form of systemic metastasis of intra-abdominal cancers, occurring in as many as 50% of colon cancer patients, and is associated with a poor prognosis. For the treatment of CRPC, cytoreductive surgery alone is inadequate at the microscopic level, and systemic chemotherapy has a limited effect due to the peritoneal-plasma barrier. Intraperitoneal chemotherapy is logically proposed early after surgery to treat the residual small and microscopic tumors. Traditional chemotherapy is typically infused intravenously. However, intraperitoneal chemotherapy allows direct contact of anti-cancer agents with tumor cells, which could improve tumor regression efficacy and minimize systemic toxicity. Furthermore, injectable and thermosensitive polymer hydrogels have shown promising applications as controlled drug delivery systems for in situ chemotherapy. In this study, a biodegradable thermogelling block copolymer poly(L-lactide acid)-Pluronic L35-poly(L-lactide acid) (PLLA-L35-PLLA) was synthesized to fabricate a novel local drug delivery system (DOC-M/OXA-H) composed of docetaxel loaded micelles (DOC-M) and an oxaliplatin loaded hydrogel (OXA-H). DOC, a widely used anticancer drug with extremely high hydrophobicity, was loaded into the biodegradable copolymer micelles by the membrane dialysis method without using any surfactants or excipients. And DOC-M was encapsulated in OXA-H to achieve the aim of synergistic combination therapy with significantly high efficacy and good patient compliance. As a result, DOC-M/OXA-H was an injectable flowing sol at ambient temperature and became a solid-like gel at physiological temperature without any crosslinking agent. Meanwhile, DOC-M/OXA-H demonstrated a slow and sustained drug release profile and the combination therapy of DOC and OXA exhibited quite potent cytotoxicity in vitro. Furthermore, an in vivo antitumor test with CRPC-bearing mice suggested that DOC-M/OXA-H was more competent for suppressing tumor growth and prolonging survival time by inhibiting tumor cell proliferation and angiogenesis and increasing apoptosis of tumor cells. Overall, our data suggested that DOC-M/OXA-H may be potentially useful in the treatment of CRPC.
机译：结肠直肠腹膜癌症（CRPC）是腹部癌症的全身转移的常见形式，发生在多达50％的结肠癌患者中，并且与预后差有关。对于CRPC的治疗，仅在微观水平下单独的细胞抑菌性手术不适，并且由于腹膜 - 血浆屏障由于腹膜等离子体屏障而具有有限的效果。手术后早期提出脑内化疗，以治疗残留的小和微观肿瘤。传统化学疗法通常静脉注入。然而，腹膜内化学疗法允许直接接触抗癌剂与肿瘤细胞，这可以改善肿瘤回归疗效并最小化系统性毒性。此外，可注射和热敏聚合物水凝胶已经显示有希望的应用作为用于原位化疗的受控药物递送系统。在该研究中，合成了可生物降解的热凝胶嵌段共聚物聚（L-丙交酯）-PluronicL35-聚（L-丙交酯）（L-丙交酯）（PLLA-L35-PLLA）以制造新的局部药物递送系统（DOC-M / OXA） -H）由多西紫杉醇负载胶束（DOC-M）和奥沙利铂负载水凝胶（OXA-H）组成。 DoC是一种广泛使用具有极高疏水性的抗癌药物，通过膜透析方法装入可生物降解的共聚物胶束，而不使用任何表面活性剂或赋形剂。和Doc-M在氧气-H中封装，以实现协同组合治疗的目的，具有显着高的疗效和良好的患者依从性。结果，DOC-M / OXA-H在环境温度下是可注射的流动溶胶，并且在没有任何交联剂的生理温度下成为固体样凝胶。同时，Doc-M / Oxa-H证明了缓慢而持续的药物释放曲线，DOC和OXA的组合治疗在体外表现出相当有效的细胞毒性。此外，具有CRPC轴承小鼠的体内抗肿瘤试验表明，通过抑制肿瘤细胞增殖和血管生成和增加肿瘤细胞的凋亡，DOC-M / OXA-H更竞受抑制肿瘤生长和延长存活时间。总体而言，我们的数据表明DOC-M / OXA-H可能在治疗CRPC中可能有用。

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  • 来源
    《RSC Advances》 |2015年第123期|共13页
  • 作者

    Li Xiaoling; Fan Rangrang; Wang Yuelong; Wu Min; Tong Aiping; Shi Juan; Xiang Mingli; Zhou Liangxue; Guo Gang;

  • 作者单位

    Sichuan Univ Collaborat Innovat Ctr Biotherapy West China Hosp Dept Neurosurg State Key Lab Biotherapy Chengdu 610041 Peoples R China;

    Sichuan Univ Collaborat Innovat Ctr Biotherapy West China Hosp Dept Neurosurg State Key Lab Biotherapy Chengdu 610041 Peoples R China;

    Sichuan Univ Collaborat Innovat Ctr Biotherapy West China Hosp Dept Neurosurg State Key Lab Biotherapy Chengdu 610041 Peoples R China;

    Sichuan Univ Collaborat Innovat Ctr Biotherapy West China Hosp Dept Neurosurg State Key Lab Biotherapy Chengdu 610041 Peoples R China;

    Sichuan Univ Collaborat Innovat Ctr Biotherapy West China Hosp Dept Neurosurg State Key Lab Biotherapy Chengdu 610041 Peoples R China;

    Chinese Acad Med Sci Inst Basic Med Natl Lab Med Mol Biol Sci Beijing 100005 Peoples R China;

    Sichuan Univ Collaborat Innovat Ctr Biotherapy West China Hosp Dept Neurosurg State Key Lab Biotherapy Chengdu 610041 Peoples R China;

    Sichuan Univ Collaborat Innovat Ctr Biotherapy West China Hosp Dept Neurosurg State Key Lab Biotherapy Chengdu 610041 Peoples R China;

    Sichuan Univ Collaborat Innovat Ctr Biotherapy West China Hosp Dept Neurosurg State Key Lab Biotherapy Chengdu 610041 Peoples R China;

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