Effect of paclitaxel associated with lipidic nanoemulsions on the peribronchial and perivascular inflammatory process after unilateral left lung transplantation in rats

• Grant number: 15/21556-2
• Support Opportunities: Regular Research Grants
• Start date: June 01, 2016
• End date: November 30, 2018
• Field of knowledge: Health Sciences - Medicine - Surgery
• Principal Investigator: Rogerio Pazetti
• Grantee: Rogerio Pazetti
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated researchers: Elaine Rufo Tavares ; Francine Maria de Almeida ; Paulo Manuel Pêgo-Fernandes ; Raul Cavalcante Maranhao

Abstract

Lung transplantation (TxP) is the only alternative therapy for various diseases in advanced stadium of development, such as pulmonary emphysema, idiopathic pulmonary fibrosis and cystic fibrosis. However, several factors limit the success of TxP in later postoperative period, with a survival rate of just 53% and 30% after 5 and 10 years, respectively. Bronchiolitis obliterans (BO) is the third (4.6%) leading cause of death in the first year after TXP and the first (26%) after this period. Clinically, BO is characterized by progressive and irreversible obstruction of the distal airways and by the sharp decrease of the forced expiratory volume in one second (FEV1). Histopathologically, BO is marked by an intense peribronchial lymphocyte infiltrate, an increase in mesenchymal cells of the airways and increased extracellular matrix deposition, followed by a dense fibrous scars in lamina propria and lumen of respiratory bronchioles. Moreover, there is vascular sclerosis of the veins and pulmonary arteries. Given the difficulty in finding a solution for the treatment of BO to date, new therapeutic alternatives should be sought in the postoperative management of TxP. Accordingly, based on previous demonstration that paclitaxel incorporated into lipid nanoemulsion acts potently on the regression of vascular transplanted heart disease, we believe it could have the same effect on lung tissue, preventing or mitigating the development of BO after the TxP by reducing the peribronchial and perivascular inflammation. (AU)