title: The potential efficacy of R8-modified paclitaxel-loaded liposomes on pulmonary arterial hypertension.
abstract: OBJECTIVE
  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.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.
authors.forename: Yujia
authors.initials: Y
authors.lastname: Yin
authors.forename: Xindan
authors.initials: X
authors.lastname: Wu
authors.forename: Zhangya
authors.initials: Z
authors.lastname: Yang
authors.forename: Jian
authors.initials: J
authors.lastname: Zhao
authors.forename: Xiaoshuang
authors.initials: X
authors.lastname: Wang
authors.forename: Qianyu
authors.initials: Q
authors.lastname: Zhang
authors.forename: Mingqing
authors.initials: M
authors.lastname: Yuan
authors.forename: Liang
authors.initials: L
authors.lastname: Xie
authors.forename: Hanmin
authors.initials: H
authors.lastname: Liu
authors.forename: Qin
authors.initials: Q
authors.lastname: He
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D065627:Familial Primary Pulmonary Hypertension; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000473:pathology; D008081:Liposomes / Q000737:chemistry* / Q000378:metabolism; D008168:Lung / Q000098:blood supply / Q000187:drug effects / Q000473:pathology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology; D009842:Oligopeptides / Q000737:chemistry* / Q000378:metabolism; D017239:Paclitaxel / Q000008:administration & dosage* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D050257:Tubulin Modulators / Q000008:administration & dosage* / Q000627:therapeutic use
chemical_list: D008081:Liposomes; D009842:Oligopeptides; D050257:Tubulin Modulators; C448619:octaarginine; D017239:Paclitaxel