Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 20, Issue 23, Pages -Publisher
MDPI
DOI: 10.3390/ijms20235885
Keywords
pulmonary arterial hypertension; prostaglandin I-2; nitric oxide; endothelin
Funding
- Ministry of Education, Culture, Sports, Science and Technology, Tokyo, Japan [15K09158, 18K08037]
- Japan Agency for Medical Research and Development [18950119]
- Grants-in-Aid for Scientific Research [15K09158, 18K08037] Funding Source: KAKEN
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There are three critical pathways for the pathogenesis and progression of pulmonary arterial hypertension (PAH): the prostacyclin (prostaglandin I-2) (PGI(2)), nitric oxide (NO), and endothelin pathways. The current approved drugs targeting these three pathways, including prostacyclin (PGI(2)), 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 (PGI(2)) 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.
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