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The Potential Efficacy of R8-Modified Paclitaxel-Loaded Liposomes on Pulmonary Arterial Hypertension.
MedLine Citation:
PMID:  23756757     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
PURPOSE: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.
Authors:
Yujia Yin; Xindan Wu; Zhangya Yang; Jian Zhao; Xiaoshuang Wang; Qianyu Zhang; Mingqing Yuan; Liang Xie; Hanmin Liu; Qin He
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-6-12
Journal Detail:
Title:  Pharmaceutical research     Volume:  -     ISSN:  1573-904X     ISO Abbreviation:  Pharm. Res.     Publication Date:  2013 Jun 
Date Detail:
Created Date:  2013-6-12     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8406521     Medline TA:  Pharm Res     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
The Pulmonary Vascular Remodeling Research Unit Department of Pediatric, West China Second University Hospital, Sichuan University, No. 20, Section 3, RenminNanLu Road, Chengdu, Sichuan, 610041, People's Republic of China.
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