Proposed PAH Drug Delivery System Allows for Controlled Release of Medicine
Researchers at the National University of Singapore (NUS) and the Agency for Science, Technology and Research (A*STAR) have developed an alternative treatment system for patients with pulmonary arterial hypertension (PAH), consisting of a controlled-release microparticle formulation that’s delivered through inhalation. The article reporting the system’s development was published in the journal Current Pharmaceutical Design and titled “Controlled Release Inhalable Polymeric Microspheres for Treatment of Pulmonary Arterial Hypertension.”
Current treatments for PAH are based on several classes of drugs, which include endothelin receptor antagonists (ERAs) and phosphodiesterase-5 (PDE-5) inhibitors. Prostanoid drugs, the most effective treatment, target the prostacylin pathway, and aim to correct the deficiency on endogenous prostacyclin (a potent vasodilator) seen in PAH patients. The therapeutic agent is delivered through intravenous infusion or inhalation solution, dilating the systemic and pulmonary arteries.
Despite its clinical effectiveness, the major disadvantage of prostanoid drugs is their short half-lives, resulting in a need for administration six to about nine times a day and a general poor compliance to medication. Several strategies of controlled-released inhalation treatments have been developed, including liposomes, biodegradable nano and microparticles, formation of co-precipitates and complexation with cyclodextrins.
Based on this knowledge, the research team at NUS developed an inhaled formulation that consists of polymeric microspheres designed to reside in the lung for a longer period of time. Importantly, these microspheres allow the release of therapeutic agents, in the site of drug action, at a slow, paced, steady and consistent rate, overcoming the short-life hurdle of other treatment options. Furthermore, this method could reduce dosing frequency, improving compliance with treatment.
If further tests provide positive results and the formulation is approved, this pharmaceutical product would be the first commercially available controlled-release inhalation product.
PAH is a life-threatening chronic disease characterized by high blood pressure, vascular resistance, and abnormal constriction of the pulmonary artery. The condition causes the heart to work faster and elevates blood pressure in arteries within the lungs, potentially causing fatal heart failure and other, less serious, complications and disturbances in quality of life. Currently, there is no cure for the condition.