Fasudil and SOD packaged in peptide-studded-liposomes: Properties, pharmacokinetics and ex-vivo targeting to isolated perfused rat lungs.
Fasudil and SOD packaged in peptide-studded-liposomes: Properties, pharmacokinetics and ex-vivo targeting to isolated perfused rat lungs.
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DOI：
10.1016/j.ijpharm.2015.04.031
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发表时间：
2015-07-05
影响因子：
5.8
通讯作者：
Ahsan, Fakhrul
中科院分区：
文献类型：
--
作者：
Gupta, Nilesh;Al-Saikhan, Fahad I.;Patel, Brijeshkumar;Rashid, Jahidur;Ahsan, Fakhrul
本研究探讨了法舒地尔和超氧化物歧化酶（SOD）两种药物包封在脂质体中靶向吸入给药至肺血管治疗肺动脉高压（PAH）的可行性。采用薄膜挤压法制备纳米脂质体，采用改良的冻融技术对药物进行包封。肽CARSKNKDC (CAR)，肺特异性靶向序列，偶联在脂质体表面。优化制剂的各种理化性质，测试其气管内给药后的体外和体内药物吸收，并评估健康大鼠的短期安全性。匀相纳米脂质体含有超氧化物歧化酶（~55%包裹度）和法舒地尔（~40%包裹度），在4℃和雾化后稳定。脂质体以控释方式释放药物。与普通脂质体相比，car -脂质体使肺内皮细胞和平滑肌细胞的摄取增加约2倍。car脂质体使SOD和法舒地尔的生物半衰期延长了3倍。离体研究表明，car -脂质体比普通脂质体在肺中保留得更好。支气管肺泡灌洗研究表明，配备肽的脂质体作为肺输送载体是安全的。总之，本研究表明car -脂质体可作为吸入载体，用于SOD +法舒地尔联合治疗PAH。
The present study investigated the feasibility of encapsulating two drugs, fasudil and superoxide dismutase (SOD), into liposomes for targeted and inhalational delivery to the pulmonary vasculature to treat pulmonary arterial hypertension (PAH). Nanosized liposomes were prepared by a thin-film formation and extrusion method, and the drugs were encapsulated by a modified freeze-thaw technique. The peptide CARSKNKDC (CAR), a pulmonary-specific targeting sequence, was conjugated on the surface of liposomes. Formulations were optimized for various physicochemical properties, tested for their ex-vivo and in-vivo drug absorption after intratracheal administration, and evaluated for short-term safety in healthy rats. The homogenous nanosized liposomes contained both SOD (~55% entrapment) and fasudil (~40% entrapment), and were stable at 4°C and after nebulization. Liposomes released the drugs in a controlled-release fashion. Compared with plain liposomes, CAR-liposomes increased the uptake by pulmonary endothelial and smooth muscle cells by ~2-fold. CAR-liposomes extended the biological half-lives of SOD and fasudil by ~3-fold. Ex-vivo studies demonstrated that CAR-liposomes were better retained in the lungs than plain liposomes. Bronchoalveolar lavage studies indicated the safety of peptide-equipped liposomes as pulmonary delivery carriers. Overall, this study demonstrates that CAR-liposomes may be used as inhalational carriers for SOD plus fasudil-based combination therapy for PAH.
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DOI：
10.2217/nnm.11.92
发表时间：
2011-09
期刊：
Nanomedicine (London, England)
影响因子：
--
作者：
Hood E;Simone E;Wattamwar P;Dziubla T;Muzykantov V
通讯作者：
Muzykantov V
DOI：
10.1152/ajplung.00309.2009
发表时间：
2010-07-01
影响因子：
4.9
作者：
Farrow, Kathryn N.;Lakshminrusimha, Satyan;Steinhorn, Robin H.
通讯作者：
Steinhorn, Robin H.
影响因子：
2.9
作者：
Barman SA;Zhu S;White RE
通讯作者：
White RE
影响因子：
20.1
作者：
Oka, Masahiko;Homma, Noriyuki;McMurtry, Ivan F.
通讯作者：
McMurtry, Ivan F.
影响因子：
45.3
作者：
Feldman, Eric J.;Lancet, Jeffrey E.;Louie, Arthur C.
通讯作者：
Louie, Arthur C.