An Update on Advancements and Challenges in Inhalational Drug Delivery for Pulmonary Arterial Hypertension

Abstract

A lethal condition at the arterial–alveolar juncture caused the exhaustive remodeling of pulmonary arterioles and persistent vasoconstriction, followed by a cumulative augmentation of resistance at the pulmonary vascular and, consequently, right-heart collapse. The selective dilation of the pulmonary endothelium and remodeled vasculature can be achieved by using targeted drug delivery in PAH. Although 12 therapeutics were approved by the FDA for PAH, because of traditional non-specific targeting, they suffered from inconsistent drug release. Despite available inhalation delivery platforms, drug particle deposition into the microenvironment of the pulmonary vasculature and the consequent efficacy of molecules are influenced by pathophysiological conditions, the characteristics of aerosolized mist, and formulations. Uncertainty exists in peripheral hemodynamics outside the pulmonary vasculature and extra-pulmonary side effects, which may be further exacerbated by underlying disease states. The speedy improvement of arterial pressure is possible via the inhalation route because it has direct access to pulmonary arterioles. Additionally, closed particle deposition and accumulation in diseased tissues benefit the restoration of remolded arterioles by reducing fallacious drug deposition in other organs. This review is designed to decipher the pathological changes that should be taken into account when targeting the underlying pulmonary endothelial vasculature, especially with regard to inhaled particle deposition in the alveolar vasculature and characteristic formulations.

Tadalafil Nanoemulsion Mists for Treatment of Pediatric Pulmonary Hypertension via Nebulization

“…Many efforts have been made to overcome the limitations accompanying the conventional treatment using anti-PAH drugs and improve their efficacy through employing novel drug delivery systems, including liposomes, polymeric nanoparticles, solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs), micelles and nano-erythrosomes [6,7]. However, nanoemulsions (NEs) were chosen in the current study as they proved efficacy in the pulmonary delivery of poorly soluble drugs [8][9][10][11][12][13][14][15][16].…”

Therapeutic Use of an Inhaled Drug Delivery in Pulmonary Hypertension: A Review

“…Pulmonary hypertension (PH) can be classified as pre-or post-capillary PH. Precapillary PH occurs due to a primary elevation of pressure in the pulmonary precapillary PH (e.g., PAH), while post-capillary PH occurs due to elevations of pressure in the pulmonary venous and pulmonary capillary systems (pulmonary venous hypertension) [1]. There may be a rise of over 25 mmHg pressure in pulmonary artery.…”

“…The mean pulmonary artery pressure (mPAP) is elevated by around 30 mmHg hemodynamically, while usual left ventricular refilling pressures are maintained. The mPAP, however, is 25 mmHg at rest [1]. Elevated pulmonary vascular resistance (PVR), brought on due to unchecked pulmonary vascular restructuring, is a pathologic characteristic of this condition.…”