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载紫杉醇的核壳结构固体脂质毫微粒用于卵巢癌腹腔化疗的持续释放。

Sustained release paclitaxel-loaded core-shell-structured solid lipid microparticles for intraperitoneal chemotherapy of ovarian cancer.

机构信息

a Department of Precision Machinery and Precision Instrumentation, School of Engineering Science , University of Science and Technology of China , Hefei , P.R.China.

b Department of Chemistry, Laboratory of Nanomaterials for Energy Conversion (LNEC) , University of Science and Technology of China , Hefei , Anhui, PR China.

出版信息

Artif Cells Nanomed Biotechnol. 2019 Dec;47(1):957-967. doi: 10.1080/21691401.2019.1576705.

Abstract

The current clinical paradigm for ovarian cancer treatment has a poor prognosis, partially due to the efficacy and toxicity concerns associated with the available chemotherapeutic formulations. To overcome these limitations, we have designed core-shell-structured paclitaxel (PTX) laden solid lipid microparticles (PTX-SLMPs) for intraperitoneal treatment of ovarian cancer. A single-step coaxial electro hydrodynamic atomization (CEHDA) process has been explored to synthesize core-shell structure of PTX-SLMPs with the particle size of 1.76 ± 0.37 µm. Core-shell PTX-SLMPs have high encapsulation efficiency of 94.73% with sustained drug release profile. In vitro evaluation of PTX-SLMPs in SKOV-3 ovarian cancer cells yield significant enhancement in cytotoxicity when compared with Taxol®. In vivo pharmacokinetic study demonstrated slower absorption of PTX into the systemic circulation after intraperitoneal (i.p.) administration of PTX-SLMPs in Wistar rats implying the PTX-SLMPs remained in the peritoneal cavity and released the PTX for prolonged period of time. Through these studies, we have demonstrated the technical potential of core-shell structured PTX-SLMPs, which can enhance passive targeting of PTX to the tumor in the treatment of not only ovarian cancer but also in other peritoneal cancer.

摘要

目前卵巢癌治疗的临床模式预后较差,部分原因是由于现有化疗制剂的疗效和毒性问题。为了克服这些限制,我们设计了载紫杉醇(PTX)的核壳结构固体脂质毫微粒(PTX-SLMPs),用于治疗卵巢癌的腹腔内治疗。探索了一步同轴电动力学雾化(CEHDA)工艺,以合成粒径为 1.76±0.37μm 的核壳结构的 PTX-SLMPs。PTX-SLMPs 的包封效率高达 94.73%,具有持续的药物释放特性。与 Taxol®相比,PTX-SLMPs 在 SKOV-3 卵巢癌细胞中的体外评估显示出显著增强的细胞毒性。在 Wistar 大鼠中的体内药代动力学研究表明,PTX-SLMPs 经腹腔给药后,PTX 进入体循环的吸收速度较慢,这意味着 PTX-SLMPs 仍留在腹腔内,并在较长时间内释放 PTX。通过这些研究,我们证明了核壳结构的 PTX-SLMPs 具有技术潜力,可增强 PTX 对肿瘤的被动靶向作用,不仅可用于治疗卵巢癌,还可用于治疗其他腹膜癌。

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