Abstract 15695: Nanoparticle-Mediated Drug Delivery System of Prostaglandin I2 Into Lungs Ameliorates the Development of Monocrotaline-Induced Pulmonary Artery Hypertension in Rats
Background: Intravenous prostaglandin I2 (PGI2) improves hemodynamics and long-term survival in patients with pulmonary arterial hypertension (PAH). However, systemic intravenous infusion of PGI2 causes flashing, headache and catheter-related infections. Nanoparticles (NP) have properties of local drug delivery and sustained drug release. We investigated the effects of NP-mediated delivery of PGI2 (PGI2-NP) into the lungs in a rat model of PAH.
Methods: Rats were received a single intratracheal administration of PBS, FITC-NP or PGI2-NP 14 days after monocrotaline injection. Hemodynamics, right ventricular (RV) hypertrophy and pulmonary artery muscularization were assessed 28 days after monocrotaline injection. We examined survival rates after single administration of PBS or PGI2-NP.
Results: After single administration, PGI2-NP significantly decreased RV pressure (PGI2-NP: 63±15 mmHg, FITC-NP: 87±13 mmHg, PBS: 84±11 mmHg) (Figure 1), RV hypertrophy (RV/LV+S ratio; PGI2-NP: 0.39±0.11, FITC-NP: 0.59±0.09, PBS: 0.54±0.07) (Figure 2) and pulmonary artery muscularization (percentage of fully-muscularized small pulmonary artery; PGI2-NP: 37±6%, FITC-NP: 70±3%, PBS: 63±7%). PGI2-NP significantly improved survival rate (PGI2-NP: 65.0% and PBS: 27.8%, P <0.05).
Conclusion: PGI2-NP into lungs ameliorates the development of the monocrotaline-induced PAH in rats. Inhaled PGI2-NP might develop as a novel approach for treatment of PAH.
- © 2013 by American Heart Association, Inc.