Nanoparticle-based therapy for respiratory diseases

Silva, Adriana L. da; Santos, Rodrigues dos; Xisto, Débora G.; Alonso, Silvia del Valle; Morales, Marcelo M.; Rocco, Patrícia Rieken Macêdo

doi:10.1590/s0001-37652013005000018

Cited by 37 publications

(23 citation statements)

References 51 publications

(36 reference statements)

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“…The increase in NP size beyond the average mucus mesh spacing size, as observed in PBAE-CPs, hinders the diffusion of PBAE-CPs in the airway mucus, leading to rapid clearance by MCC before they reach the airway epithelium. Furthermore, particle aggregates deposited in the airspace are likely engulfed by alveolar macrophages and subsequently cleared from the lung (35)(36)(37). This formulation strategy can be generalized to formulate PBAEMPPs with various leading core PBAE polymers ( Fig.…”

Section: Resultsmentioning

confidence: 99%

Highly compacted biodegradable DNA nanoparticles capable of overcoming the mucus barrier for inhaled lung gene therapy

Mastorakos

Silva

Chisholm

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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167

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Gene therapy has emerged as an alternative for the treatment of diseases refractory to conventional therapeutics. Synthetic nanoparticle-based gene delivery systems offer highly tunable platforms for the delivery of therapeutic genes. However, the inability to achieve sustained, high-level transgene expression in vivo presents a significant hurdle. The respiratory system, although readily accessible, remains a challenging target, as effective gene therapy mandates colloidal stability in physiological fluids and the ability to overcome biological barriers found in the lung. We formulated highly stable DNA nanoparticles based on state-of-theart biodegradable polymers, poly(β-amino esters) (PBAEs), possessing a dense corona of polyethylene glycol. We found that these nanoparticles efficiently penetrated the nanoporous and highly adhesive human mucus gel layer that constitutes a primary barrier to reaching the underlying epithelium. We also discovered that these PBAE-based mucus-penetrating DNA nanoparticles (PBAE-MPPs) provided uniform and high-level transgene expression throughout the mouse lungs, superior to several gold standard gene delivery systems. PBAE-MPPs achieved robust transgene expression over at least 4 mo following a single administration, and their transfection efficiency was not attenuated by repeated administrations, underscoring their clinical relevance. Importantly, PBAE-MPPs demonstrated a favorable safety profile with no signs of toxicity following intratracheal administration.lung gene therapy | mucus-penetrating particles | nanotechnology | biodegradable polymer | nonviral gene delivery

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Section: Resultsmentioning

confidence: 99%

Highly compacted biodegradable DNA nanoparticles capable of overcoming the mucus barrier for inhaled lung gene therapy

Mastorakos

Silva

Chisholm

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

167

151

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“…However, a number of factors can influence the effects of nanoparticles in the lung, such as physical characteristics and toxicity, routes of administration, and lung physiology in the presence of respiratory diseases [23]. Especially, some nanoparticles are found to have adverse effects in animal models.…”

Section: Nanoparticle Therapy In Lung Diseasesmentioning

confidence: 99%

Right or Left: The Role of Nanoparticles in Pulmonary Diseases

Zhu

Chen

et al. 2014

IJMS

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Due to the rapid development of the nanotechnology industry in the last decade, nanoparticles (NPs) are omnipresent in our everyday life today. Many nanomaterials have been engineered for medical purposes. These purposes include therapy for pulmonary diseases. On other hand, people are endeavoring to develop nanomaterials for improvement or replacement of traditional therapies. On the other hand, nanoparticles, as foreign material in human bodies, are reported to have potential adverse effects on the lung, including oxidase stress, inflammation, fibrosis and genotoxicity. Further, these damages could induce pulmonary diseases and even injuries in other tissues. It seems that nanoparticles may exert two-sided effects. Toxic effects of nanomaterials should be considered when their use is developed for therapies. Hence this review will attempt to summarize the two-side roles of nanoparticles in both therapies for pulmonary diseases and initiation of lung diseases and even secondary diseases caused by lung injuries. Determinants of these effects such as physicochemical properties of nanoparticles will also be discussed.

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“…Nanoparticles have emerged as an exciting alternative to accommodate the requirements for delivering active Wnts to the lungs. Given their small size, aerosolized nanoparticles can be delivered to the distal airspaces effectively and to release encapsulated compounds locally with limited systemic effects [46]. Although no studies have yet been done looking at Wnt delivery to the lung, there have been reports demonstrating that Wnt3a packaged in liposomal particles has intact biological activity and can activate Wnt/bC signaling, as evidenced by luciferase production in cell lines transfected with bC luciferase reporter [47].…”

Section: Use Of Biological Therapiesmentioning

confidence: 99%

Targeting the Wnt signaling pathways in pulmonary arterial hypertension

Perez

Yuan

Alastalo

et al. 2014

Drug Discovery Today

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Pulmonary arterial hypertension (PAH) is a life-threatening disorder that is associated with elevated pulmonary pressures and right heart failure resulting from progressive loss and thickening of small pulmonary arteries. Despite their ability to improve symptoms, current therapies fail to prevent disease progression, leaving lung transplantation as the only therapy in end-stage PAH. To overcome the limitations of current therapies, there is an active search for disease-modifying agents capable of altering the natural history of, and improving clinical outcomes in, PAH. The Wnt signaling pathways have emerged as attractive treatment targets in PAH given their role in the preservation of pulmonary vascular homeostasis and the recent development of Wnt-specific compounds and biological therapies capable of modulating pathway activity. In this review, we summarize the literature describing the role of Wnt signaling in the pulmonary circulation and discuss promising advances in the field of Wnt therapeutics that could lead to novel clinical therapies capable of preventing and/or reversing pulmonary vascular pathology in patients with this devastating disease.

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Nanoparticle-based therapy for respiratory diseases

Cited by 37 publications

References 51 publications

Highly compacted biodegradable DNA nanoparticles capable of overcoming the mucus barrier for inhaled lung gene therapy

Highly compacted biodegradable DNA nanoparticles capable of overcoming the mucus barrier for inhaled lung gene therapy

Right or Left: The Role of Nanoparticles in Pulmonary Diseases

Targeting the Wnt signaling pathways in pulmonary arterial hypertension

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