title: An artificial nanoemulsion carrying paclitaxel decreases the transplant heart vascular disease: a study in a rabbit graft model.
abstract: OBJECTIVE
  In previous studies cholesterol-rich nanoemulsions (LDE) resembling low-density lipoprotein were shown to concentrate in atherosclerotic lesions of rabbits. Lesions were pronouncedly reduced by treatment with paclitaxel associated with LDE. This study aimed to test the hypothesis of whether LDE-paclitaxel is able to concentrate in grafted hearts of rabbits and to ameliorate coronary allograft vasculopathy after the transplantation procedure.
  
  
  METHODS
  Twenty-one New Zealand rabbits fed 0.5% cholesterol were submitted to heterotopic heart transplantation at the cervical position. All rabbits undergoing transplantation were treated with cyclosporin A (10 mg · kg(-1) · d(-1) by mouth). Eleven rabbits were treated with LDE-paclitaxel (4 mg/kg body weight paclitaxel per week administered intravenously for 6 weeks), and 10 control rabbits were treated with 3 mL/wk intravenous saline. Four control animals were injected with LDE labeled with [(14)C]-cholesteryl oleate ether to determine tissue uptake.
  
  
  RESULTS
  Radioactive LDE uptake by grafts was 4-fold that of native hearts. In both groups the coronary arteries of native hearts showed no stenosis, but treatment with LDE-paclitaxel reduced the degree of stenosis in grafted hearts by 50%. The arterial luminal area in grafts of the treated group was 3-fold larger than in control animals. LDE-paclitaxel treatment resulted in a 7-fold reduction of macrophage infiltration. In grafted hearts LDE-paclitaxel treatment reduced the width of the intimal layer and inhibited the destruction of the medial layer. No toxicity was observed in rabbits receiving LDE-paclitaxel treatment.
  
  
  CONCLUSIONS
  LDE-paclitaxel improved posttransplantation injury to the grafted heart. The novel therapeutic approach for heart transplantation management validated here is thus a promising strategy to be explored in future clinical studies.
authors: Heart Institute (InCor) of the University of São Paulo Medical School Hospital, São Paulo, Brazil.
authors: Domingos D
authors: DD
authors: Lourenço-Filho
authors: Raul C
authors: RC
authors: Maranhão
authors: Carlos A
authors: CA
authors: Méndez-Contreras
authors: Elaine R
authors: ER
authors: Tavares
authors: Fatima R
authors: FR
authors: Freitas
authors: Noedir A
authors: NA
authors: Stolf
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D002317:Cardiovascular Agents / Q000008:administration & dosage* / Q000737:chemistry; D023921:Coronary Stenosis / Q000097:blood / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D004337:Drug Carriers; D004655:Emulsions; D006084:Graft Rejection / Q000209:etiology / Q000473:pathology / Q000517:prevention & control; D006085:Graft Survival / Q000187:drug effects; D016027:Heart Transplantation / Q000009:adverse effects*; D008055:Lipids / Q000097:blood; D008264:Macrophages / Q000187:drug effects / Q000473:pathology; D008297:Male; D009206:Myocardium / Q000473:pathology; D053758:Nanoparticles; D017239:Paclitaxel / Q000008:administration & dosage* / Q000737:chemistry*; D011817:Rabbits; D012720:Severity of Illness Index; D013997:Time Factors
chemical_list: D002317:Cardiovascular Agents; D004337:Drug Carriers; D004655:Emulsions; D008055:Lipids; D017239:Paclitaxel