The Potential Efficacy of R8-Modified Paclitaxel-Loaded Liposomes on Pulmonary Arterial Hypertension
The Potential Efficacy of R8-Modified Paclitaxel-Loaded Liposomes on Pulmonary Arterial Hypertension
复制标题
r8 修饰的紫杉醇脂质体对肺动脉高压的潜在疗效
DOI：
10.1007/s11095-013-1058-8
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发表时间：
2013-08-01
影响因子：
3.7
通讯作者：
He, Qin
中科院分区：
文献类型：
--
作者：
Yin, Yujia;Wu, Xindan;He, Qin
在本文中，制造了用八甲甲酰胺（R8）修饰的紫杉醇的新型脂质体配方，并评估了其对肺动脉高压的治疗功效。 。通过MTT分析确定不同制剂对原代培养的VSMC的载体细胞毒性和抗增殖能力。通过流式细胞仪评估VSMC对不同制剂的摄取能力，并通过用若丹明 - 甲状腺素染色来研究对脂质体细胞骨架的影响。使用近红外荧光团通过CCD摄像头对脂质体的生物分布进行成像。通过血液动力学测量，右心室肥大参数和血管直径评估了不同PTX的PTX形成的治疗功效。与其他组相比，R8改性脂质体（R8-LIP）的细胞摄取可改善R8改性脂质体（R8-LIP）的细胞摄取。所有脂质体在24小时内均未在VSMC上施加细胞毒性。 R8-PTX-LIP对所有制剂中VSMC的增殖表现出最强的抑制作用（P <0.001）。 R8-PTX-LIP可以逆转表型转化，并抑制细胞迁移。 MPAP，（RV/LV+S）和用R8-PTX-LIP处理的大鼠小远端肺动脉的壁厚明显低于其他组的大鼠（P <0.001）。结论，R8的药物输送系统我们确定的 - 修饰的紫杉醇负载的脂质体在体外表现出明显的抑制作用和VSMC的增殖和细胞骨架形成，体内具有更强的肺部递送能力，并且对PAH有效，显示出对PAH治疗的肺部药物递送系统的潜力。
In this paper, a novel liposomal formulation of paclitaxel modified with octaarginine (R8) was fabricated and the therapeutic efficacy of it on pulmonary arterial hypertension was evaluated.Octaarginine-modified stealth liposomes loaded with PTX (R8-PTX-LIP) were prepared and characterized. Vector cytoxicity and anti-proliferation ability of different formulations on primary cultured VSMCs were determined with MTT assay. The uptake capacity of VSMCs on different formulations were evaluated by flow cytometry, and the influences on cytoskeletons of liposomes were investigated by cytoskeleton staining with rhodamine-phalloidin. The biodistribution of liposomes were imaged by a CCD camera using a near-infrared fluorophore DiD. The therapeutic efficacy of different PTX-formulations of PAH was evaluated by hemodynamic measurement, right ventricular hypertrophic parameters and vessel diameters.The cellular uptake of R8 modified liposomes (R8-LIP) was improved noticeably compared with other groups. All liposomes did not exert cytotoxicity on VSMCs in 24 h. R8-PTX-LIP exhibited the strongest inhibitory effect on the proliferation of VSMCs among all the formulations (p < 0.001). R8-PTX-LIP could reverse the phenotype transformation, and inhibit cell migration. mPAP, (RV/LV+S) and the wall thickness of small distal pulmonary arteries of rats treated with R8-PTX-LIP were significantly lower than those from other groups (p < 0.001).In conclusion, the drug delivery system of R8-modified paclitaxel-loaded liposomes we established showed pronounced inhibitory effect over VSMCs proliferation and cytoskeleton formation in vitro, a stronger pulmonary delivery ability in vivo, and was effective on PAH, showing the potential for pulmonary drug delivery system for PAH treatment.