Therapeutic Arteriogenesis/Angiogenesis for Peripheral Arterial Disease by Nanoparticle-Mediated Delivery of Pitavastatin into Vascular Endothelial Cells

Matsumoto, Takuya; Yoshino, Shinichiro; Kurose, Shun; Morisaki, Koichi; Nakano, K.; Koga, Jun-ichiro; Furuyama, Tadashi; Mori, Masaki; Egashira, Kensuke

doi:10.3400/avd.ra.19-00130

Cited by 15 publications

(17 citation statements)

References 20 publications

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“…Therapeutic angiogenesis is a milestone in PAD treatment, and reparative collateral growth was attempted over the years with early pioneering reports refuted by later studies [ 93 ]. Bioabsorbable poly-lactic-co-glycolic acid (PLGA) nanoparticles loaded with pitavastatin produced encouraging results in preclinical settings.…”

Section: Resultsmentioning

confidence: 99%

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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%

“…Also, the use of nanoparticle-based delivery increases the collateralization with a less than 10% cumulative dose compared to systemic administration [ 59 , 60 ]. Pitavastatin-loaded PLGA was used in a phase 1 clinical trial [ 93 ] in patients with PAD, but no specific results were reported.…”

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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“…Efficacy was also demonstrated in a rabbit model 18) and a cynomolgus monkey model of chronic lower limb ischemia 19) . Repeated intramuscular administration began 4 weeks after the induction of lower limb ischemia in the monkey model, and 6-day repeated intramuscular administration demonstrated a higher development of collateral circulation than the 1-or 3-day repeated administration.…”

Section: Introductionmentioning

confidence: 95%

Pitavastatin-Incorporated Nanoparticles for Chronic Limb Threatening Ischemia: A Phase I/IIa Clinical Trial

Matsumoto

Yoshino

Furuyama

et al. 2022

JAT

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To assess the results of a phase I/IIa open-label dose-escalation clinical trial of 5-day repeated intramuscular administration of pitavastatin-incorporated poly (lactic-co-glycolic acid) nanoparticles (NK-104-NP) in patients with chronic limb threatening ischemia (CLTI).Methods: NK-104-NP was formulated using an emulsion solvent diffusion method. NK-104-NP at four doses (nanoparticles containing 0.5, 1, 2, and 4 mg of pitavastatin calcium, n 4 patients per dose) was investigated in a dose-escalation manner and administered intramuscularly into the ischemic limbs of 16 patients with CLTI. The safety and therapeutic efficacy of treatment were investigated over a 26-week follow-up period.Results: No cardiovascular or other serious adverse events caused by NK-104-NP were detected during the follow-up period. Improvements in Fontaine and Rutherford classifications were noted in five patients (one, three, and one in the 1-, 2-, and 4-mg dose groups, respectively). Pharmacokinetic parameters including the maximum serum concentration and the area under the blood concentration-time curve increased with pitavastatin treatment in a dose-dependent manner. The area under the curve was slightly increased at day 5 compared with that at day 1 of treatment, although the difference was not statistically significant. Conclusions: This is the first clinical trial of pitavastatin-incorporated nanoparticles in patients with CLTI.Intramuscular administration of NK-104-NP to the ischemic limbs of patients with CLTI was safe and well tolerated and resulted in improvements in limb function.therapeutic angiogenesis involved the local administration of recombinant growth factor proteins 1,2) or gene-encoding growth factors [3][4][5][6] to endothelial cells. Since then, autologous stem cells 7) , endothelial progenitor cell transplantation therapy 8) , and novel nucleic acid analogs 9) have been developed.Peripheral arterial disease is a typical phenotype of progressive and systemic atherosclerosis, leading to Copyright©2021 Japan Atherosclerosis Society This article is distributed under the terms of the latest version of CC BY-NC-SA defined by the Creative Commons Attribution License.

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“…Through the knowledge gained about the complex processes involved in angiogenesis and the pioneer work of therapeutic angiogenesis by Judah Folkman (1974) [1,47], many pro-angiogenic therapeutic approaches have been applied in the CLI treatment. Currently, several clinical and preclinical studies have supported the safety and clinical potential of treating CLI through pro-angiogenic therapeutic interventions [111][112][113][114][115][116][117]. These pro-angiogenic interventions are based on the involvement of growth factors such as VEGF [117], cell-based strategies, exosomes, miRs, proteins and gene therapy [23,112,116,118,119].…”

Section: Angiogenesis In Critical Limb Ischemiamentioning

confidence: 99%

Pro-angiogenic approach for skeletal muscle regeneration

Floriano

Costa

Vega

et al. 2022

Biochimica et Biophysica Acta (BBA) - General Subjects

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Therapeutic Arteriogenesis/Angiogenesis for Peripheral Arterial Disease by Nanoparticle-Mediated Delivery of Pitavastatin into Vascular Endothelial Cells

Cited by 15 publications

References 20 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

Pitavastatin-Incorporated Nanoparticles for Chronic Limb Threatening Ischemia: A Phase I/IIa Clinical Trial

Pro-angiogenic approach for skeletal muscle regeneration

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