This study sought to investigate the efficacy of a noninvasive and long acting polymeric particle based formulation of
prostaglandin E1 (
PGE1), a potent pulmonary
vasodilator, in alleviating the signs of
pulmonary hypertension (PH) and reversing the biochemical changes that occur in the diseased lungs. PH rats, developed by a single
subcutaneous injection of
monocrotaline (MCT), were treated with two types of polymeric particles of
PGE1, porous and nonporous, and intratracheal or intravenous plain
PGE1. For chronic studies, rats received either intratracheal porous
poly(lactic-co-glycolic acid) (PLGA) particles, once- or thrice-a-day, or plain
PGE1 thrice-a-day for 10 days administered intratracheally or intravenously. The influence of formulations on
disease progression was studied by measuring the mean pulmonary arterial pressure (MPAP), evaluating
right ventricular hypertrophy and assessing various molecular and cellular makers including the degree of muscularization, platelet aggregation,
matrix metalloproteinase-2 (MMP-2), and
proliferating cell nuclear antigen (
PCNA). Both plain
PGE1 and large porous particles of
PGE1 reduced MPAP and
right ventricular hypertrophy (RVH) in rats that received the treatments for 10 days. Polymeric porous particles of
PGE1 produced the same effects at a reduced dosing frequency compared to plain
PGE1 and caused minimal off-target effects on systemic hemodynamics. Microscopic and immunohistochemical studies revealed that porous particles of
PGE1 also reduced the degree of muscularization,
von Willebrand factor (vWF), and
PCNA expression in the lungs of PH rats. Overall, our study suggests that
PGE1 loaded inhalable particulate formulations improve PH symptoms and arrest the progression of disease at a reduced dosing frequency compared to plain
PGE1.