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

Nakamura, Kazufumi; Akagi, Satoshi; Ejiri, Kentaro; Yoshida, Masashi; Miyoshi, Toru; Toh, Norihisa; Nakagawa, Koji; Takaya, Yoichi; Matsubara, Hiromi; Ito, Hiroshi

doi:10.3390/ijms20235885

Cited by 21 publications

(15 citation statements)

References 64 publications

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“…Other interesting reports were published about pulmonary artery hypertension [ 96 ]. In two studies, poliylactide-glycolide mediated pitavastatin delivery was able to reduce the progression of pulmonary artery hypertension in animal models through anti-inflammatory and antiproliferative effects [ 97 , 98 ].…”

Section: Resultsmentioning

confidence: 99%

Polymers and Nanoparticles for Statin Delivery: Current Use and Future Perspectives in Cardiovascular Disease

et al. 2021

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Atherosclerosis-related coronary artery disease (CAD) is one of the leading sources of mortality and morbidity in the world. Primary and secondary prevention appear crucial to reduce CAD-related complications. In this scenario, statin treatment was shown to be clinically effective in the reduction of adverse events, but systemic administration provides suboptimal results. As an attempt to improve bioavailability and effectiveness, polymers and nanoparticles for statin delivery were recently investigated. Polymers and nanoparticles can help statin delivery and their effects by increasing oral bioavailability or enhancing target-specific interaction, leading to reduced vascular endothelial dysfunction, reduced intimal hyperplasia, reduced ischemia-reperfusion injury, increased cardiac regeneration, positive remodeling in the extracellular matrix, reduced neointimal growth and increased re-endothelization. Moreover, some innovative aspects described in other cardiovascular fields could be translated into the CAD scenario. Recent preclinical studies are underlining the effect of statins in the stimulation and differentiation of endogenous cardiac stem cells, as well as in targeting of local adverse conditions implicated in atherosclerosis, and statin delivery through poly-lactic-co-glycolic acid (PLGA) appears the most promising aspect of current research to enhance drug activity. The present review intends to summarize the current evidence about polymers and nanoparticles for statin delivery in the field of cardiovascular disease, trying to shed light on this topic and identify new avenues for future studies.

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Section: Resultsmentioning

confidence: 99%

Polymers and Nanoparticles for Statin Delivery: Current Use and Future Perspectives in Cardiovascular Disease

et al. 2021

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“…The application of nanoparticles (NPs), a novel class of drug delivery systems used for the transport of drugs to target organs, has opened new horizons in the treatment of CVDs, and particularly PAH. Treatment with established vasodilators such as prostacyclin (PGI 2 ), Endothelin Receptor Antagonists (ERAs), Phosphodiesterase Type 5 (PDE5) Inhibitors, and Soluble Guanylate Cyclase (sGC) Stimulator‑loaded NPs have been reported to be effective both in vitro and in experimental PAH models in vivo [ 116 ]. Recently, gene therapies utilizing NPs have been also tested for PAH.…”

Section: Gene‑delivery Approaches and Gene Therapymentioning

confidence: 99%

Genetic Delivery and Gene Therapy in Pulmonary Hypertension

Rai

Shihan

Seeger

et al. 2021

IJMS

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Pulmonary hypertension (PH) is a progressive complex fatal disease of multiple etiologies. Hyperproliferation and resistance to apoptosis of vascular cells of intimal, medial, and adventitial layers of pulmonary vessels trigger excessive pulmonary vascular remodeling and vasoconstriction in the course of pulmonary arterial hypertension (PAH), a subgroup of PH. Multiple gene mutation/s or dysregulated gene expression contribute to the pathogenesis of PAH by endorsing the proliferation and promoting the resistance to apoptosis of pulmonary vascular cells. Given the vital role of these cells in PAH progression, the development of safe and efficient-gene therapeutic approaches that lead to restoration or down-regulation of gene expression, generally involved in the etiology of the disease is the need of the hour. Currently, none of the FDA-approved drugs provides a cure against PH, hence innovative tools may offer a novel treatment paradigm for this progressive and lethal disorder by silencing pathological genes, expressing therapeutic proteins, or through gene-editing applications. Here, we review the effectiveness and limitations of the presently available gene therapy approaches for PH. We provide a brief survey of commonly existing and currently applicable gene transfer methods for pulmonary vascular cells in vitro and describe some more recent developments for gene delivery existing in the field of PH in vivo.

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“…Additional studies have shown that nanoparticle therapy may be effective for patients currently on vasodilators such as prostacyclin or phosphodiesterase 5 (PDE5) inhibitors. Because intravenous administration of these drugs causes adverse effects such as headaches, hypotension, and Cather-related infection, nanoparticle-mediated Drug Delivery Systems (Nano-DDS) may circumvent repeated administration of vasodilators by allowing more efficient drug delivery mechanisms and uptake by targeted tissues [ 171 ]. The intratracheal delivery of aerosolized beraprost NPs to the lungs of MCT-induced rats reduced RV pressure, RV hypertrophy, pulmonary artery muscularization, and vascular remodeling with a single intratracheal administration.…”

Section: Precision Medicinementioning

confidence: 99%

Molecular and Genetic Profiling for Precision Medicines in Pulmonary Arterial Hypertension

Fazal

Bisserier

Hadri

2021

Cells

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Pulmonary arterial hypertension (PAH) is a rare and chronic lung disease characterized by progressive occlusion of the small pulmonary arteries, which is associated with structural and functional alteration of the smooth muscle cells and endothelial cells within the pulmonary vasculature. Excessive vascular remodeling is, in part, responsible for high pulmonary vascular resistance and the mean pulmonary arterial pressure, increasing the transpulmonary gradient and the right ventricular “pressure overload”, which may result in right ventricular (RV) dysfunction and failure. Current technological advances in multi-omics approaches, high-throughput sequencing, and computational methods have provided valuable tools in molecular profiling and led to the identification of numerous genetic variants in PAH patients. In this review, we summarized the pathogenesis, classification, and current treatments of the PAH disease. Additionally, we outlined the latest next-generation sequencing technologies and the consequences of common genetic variants underlying PAH susceptibility and disease progression. Finally, we discuss the importance of molecular genetic testing for precision medicine in PAH and the future of genomic medicines, including gene-editing technologies and gene therapies, as emerging alternative approaches to overcome genetic disorders in PAH.

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

Cited by 21 publications

References 64 publications

Polymers and Nanoparticles for Statin Delivery: Current Use and Future Perspectives in Cardiovascular Disease

Polymers and Nanoparticles for Statin Delivery: Current Use and Future Perspectives in Cardiovascular Disease

Genetic Delivery and Gene Therapy in Pulmonary Hypertension

Molecular and Genetic Profiling for Precision Medicines in Pulmonary Arterial Hypertension

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