Cell permeable peptide conjugated nanoerythrosomes of fasudil prolong pulmonary arterial vasodilation in PAH rats.
Cell permeable peptide conjugated nanoerythrosomes of fasudil prolong pulmonary arterial vasodilation in PAH rats.
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DOI：
10.1016/j.ejpb.2014.10.012
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发表时间：
2014-11
期刊：
影响因子：
--
通讯作者：
Ahsan F
中科院分区：
文献类型：
--
作者：
Gupta N;Patel B;Nahar K;Ahsan F
在这项研究中，我们验证了一种假设，即一种细胞通透性多肽CARSKNKDC(CAR)，含有Rho-Kinase(ROCK)抑制剂法舒地尔的结合纳米红细胞(NERs)，能够产生持久的肺优先血管扩张。采用低渗裂解和挤压法制备了含有法舒地尔的CAR结合物，并对其体外各种理化性质进行了优化。然后，这些配方被用于研究野百合碱诱导的肺动脉高压(PAH)啮齿动物模型的血流动力学效果。卡纳斯-法舒地尔为球形，平均囊径为161.3±1.37 nm，包封率为48.81±1.96%。制剂在4°C下储存3周内稳定，药物在受控释放48小时内释放。转化生长因子-β激活的肺动脉平滑肌细胞对卡那斯-法舒地尔的摄取是后者的1.5倍。卡那斯-法舒地尔抑制ROCK活性和5-羟色胺诱导的细胞增殖。在降低肺动脉压方面，卡纳-法舒地尔气管内给药对肺的特异性比普通法舒地尔高2倍。总体而言，CAR肽嫁接的纳米红小体提供了一个新的平台，可以在不影响外周血管扩张的情况下提高Rho-Kinase抑制剂法舒地尔的治疗效果。
In this study, we tested the hypothesis that a cell permeable peptide, CARSKNKDC (CAR), conjugated nanoerythrosomes (NERs) containing fasudil, a rho-kinase (ROCK) inhibitor, produces prolonged pulmonary preferential vasodilation. CAR conjugated NERs containing fasudil were prepared by hypotonic lysis and extrusion method, optimized for various physicochemical properties in-vitro. The formulations were then used to study the hemodynamic efficacy in a monocrotaline-induced rodent model of pulmonary arterial hypertension (PAH). CAR-NERs-Fasudil was spherical in shape with an average vesicle size and entrapment efficiency of 161.3±1.37nm and 48.81±1.96%, respectively. Formulations were stable for ~3 weeks when stored at 4°C and the drug was released in a controlled fashion for >48 hrs. The uptake of CAR-NERs-Fasudil by TGF-β activated pulmonary arterial smooth muscle cell was ~1.5 fold greater than the uptake of NERs-Fasudil. CAR-NERs-Fasudil inhibited ROCK activity and 5-hydroxytryptamine induced cell proliferation. In terms of reduction of pulmonary arterial pressure, intratracheal administration of CAR-NERs-Fasudil was ~2-fold more specific to the lungs compared with plain fasudil. Overall, CAR peptide grafted nanoerythrosomes offers a new platform for improving the therapeutic efficacy of a rho-kinase inhibitor, fasudil, without affecting peripheral vasodilation.
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影响因子：
3.4
作者：
Pouliot, R;Saint-Laurent, A;Auger, M
通讯作者：
Auger, M
影响因子：
2.9
作者：
Barman SA;Zhu S;White RE
通讯作者：
White RE
DOI：
10.1016/j.jconrel.2013.01.011
发表时间：
2013-04-28
期刊：
Journal of controlled release : official journal of the Controlled Release Society
影响因子：
--
作者：
Gupta V;Gupta N;Shaik IH;Mehvar R;McMurtry IF;Oka M;Nozik-Grayck E;Komatsu M;Ahsan F
通讯作者：
Ahsan F
影响因子：
8
作者：
Tripp RA;Alvarez R;Anderson B;Jones L;Weeks C;Chen W
通讯作者：
Chen W
影响因子：
4.9
作者：
Gupta V;Gupta N;Shaik IH;Mehvar R;Nozik-Grayck E;McMurtry IF;Oka M;Komatsu M;Ahsan F
通讯作者：
Ahsan F