Current Treatment Strategies and Nanoparticle-Mediated Drug Delivery Systems for Pulmonary Arterial Hypertension

Int J Mol Sci. 2019 Nov 23;20(23):5885. doi: 10.3390/ijms20235885.


There are three critical pathways for the pathogenesis and progression of pulmonary arterial hypertension (PAH): the prostacyclin (prostaglandin I2) (PGI2), nitric oxide (NO), and endothelin pathways. The current approved drugs targeting these three pathways, including prostacyclin (PGI2), phosphodiesterase type-5 (PDE5) inhibitors, and endothelin receptor antagonists (ERAs), have been shown to be effective, however, PAH remains a severe clinical condition and the long-term survival of patients with PAH is still suboptimal. The full therapeutic abilities of available drugs are reduced by medication, patient non-compliance, and side effects. Nanoparticles are expected to address these problems by providing a novel drug delivery approach for the treatment of PAH. Drug-loaded nanoparticles for local delivery can optimize the efficacy and minimize the adverse effects of drugs. Prostacyclin (PGI2) analogue, PDE5 inhibitors, ERA, pitavastatin, imatinib, rapamycin, fasudil, and oligonucleotides-loaded nanoparticles have been reported to be effective in animal PAH models and in vitro studies. However, the efficacy and safety of nanoparticle mediated-drug delivery systems for PAH treatment in humans are unknown and further clinical studies are required to clarify these points.

Keywords: endothelin; nitric oxide; prostaglandin I2; pulmonary arterial hypertension.

Publication types

  • Review

MeSH terms

  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / analogs & derivatives
  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / therapeutic use
  • Animals
  • Cyclic Nucleotide Phosphodiesterases, Type 5 / genetics
  • Cyclic Nucleotide Phosphodiesterases, Type 5 / metabolism
  • Drug Delivery Systems / methods
  • Humans
  • Imatinib Mesylate / therapeutic use
  • Nanoparticles / chemistry*
  • Pulmonary Arterial Hypertension / drug therapy*
  • Quinolines / therapeutic use


  • Quinolines
  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
  • Imatinib Mesylate
  • Cyclic Nucleotide Phosphodiesterases, Type 5
  • pitavastatin
  • fasudil