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Nanotechnology approaches for inhalation treatment of fibrosis.

Savla R, Minko T - J Drug Target (2013)

Bottom Line: The mutation results in the accumulation of viscous mucus in multiple organs especially in the lungs, liver and pancreas.High associated morbidity and mortality is caused by CF due to the lack of effective therapies.Second, local lung delivery substantially prevents the penetration of the delivered drug into the systemic circulation limiting adverse side effects of the treatment on other organs and tissues.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey , Piscataway, NJ , USA.

ABSTRACT
Cystic fibrosis (CF) is an autosomal recessive monogenetic disease that afflicts nearly 70,000 patients worldwide. The mutation results in the accumulation of viscous mucus in multiple organs especially in the lungs, liver and pancreas. High associated morbidity and mortality is caused by CF due to the lack of effective therapies. It is widely accepted that morbidity and mortality caused by CF is primarily due to the respiratory manifestations of the disease. Consequently, several approaches were recently developed for treatment of lung complications of CF. However, the lack of effective methods for delivery and especially targeted delivery of therapeutics specifically to lung tissues and cells limits the efficiency of the therapy. Local pulmonary delivery of therapeutics has two major advantages over systemic application. First, it enhances the accumulation of therapeutics specifically in the lungs and therefore increases the efficiency of the treatment. Second, local lung delivery substantially prevents the penetration of the delivered drug into the systemic circulation limiting adverse side effects of the treatment on other organs and tissues. This review is focused on different approaches to the treatment of respiratory manifestations of CF as well as on methods of pulmonary delivery of therapeutics.

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Penetration of polystyrene 200 nm nanoparticles through CF sputum. Polystyrene nanoparticles densely coated with low MW PEG (PS-PEG) have greater penetration through CF sputum compared to non-PEGylated particles (PS). Treatment with N-acetyl cysteine (NAC) increases penetration of both coated and non-coated particles. Mean ± SD are shown. Redrawn using data from Ref. [60].
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f8: Penetration of polystyrene 200 nm nanoparticles through CF sputum. Polystyrene nanoparticles densely coated with low MW PEG (PS-PEG) have greater penetration through CF sputum compared to non-PEGylated particles (PS). Treatment with N-acetyl cysteine (NAC) increases penetration of both coated and non-coated particles. Mean ± SD are shown. Redrawn using data from Ref. [60].

Mentions: It appears to be advantageous to develop muco-inert particles to penetrate CF sputum and reach target epithelial cells. Suk et al. [59] modeled that the average mesh spacing in CF sputum was 140 ± 50 nm with a range of 60–300 nm. They further demonstrated that particles up to 200 nm in diameter that were densely coated with low molecular weight PEG traversed CF sputum up to 90-fold faster than uncoated particles with a similar size (Figure 8). In another study, transportation of these nanoparticles was examined after CF sputum was treated with N-acetylcysteine (NAC) [60]. NAC increased the average spacing between sputum mesh elements from 145 ± 50 nm to 230 ± 50 nm (Figure 9) and the transport of the densely coated 200 nm particles in CF sputum approached their theoretical speed in water. However, when NAC was used in combination with mucoadhesive cationic liposomes and polymers for gene therapy, there was no observable correction of nasal transepithelial potential difference in CF- mice [43].Figure 8.


Nanotechnology approaches for inhalation treatment of fibrosis.

Savla R, Minko T - J Drug Target (2013)

Penetration of polystyrene 200 nm nanoparticles through CF sputum. Polystyrene nanoparticles densely coated with low MW PEG (PS-PEG) have greater penetration through CF sputum compared to non-PEGylated particles (PS). Treatment with N-acetyl cysteine (NAC) increases penetration of both coated and non-coated particles. Mean ± SD are shown. Redrawn using data from Ref. [60].
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4219586&req=5

f8: Penetration of polystyrene 200 nm nanoparticles through CF sputum. Polystyrene nanoparticles densely coated with low MW PEG (PS-PEG) have greater penetration through CF sputum compared to non-PEGylated particles (PS). Treatment with N-acetyl cysteine (NAC) increases penetration of both coated and non-coated particles. Mean ± SD are shown. Redrawn using data from Ref. [60].
Mentions: It appears to be advantageous to develop muco-inert particles to penetrate CF sputum and reach target epithelial cells. Suk et al. [59] modeled that the average mesh spacing in CF sputum was 140 ± 50 nm with a range of 60–300 nm. They further demonstrated that particles up to 200 nm in diameter that were densely coated with low molecular weight PEG traversed CF sputum up to 90-fold faster than uncoated particles with a similar size (Figure 8). In another study, transportation of these nanoparticles was examined after CF sputum was treated with N-acetylcysteine (NAC) [60]. NAC increased the average spacing between sputum mesh elements from 145 ± 50 nm to 230 ± 50 nm (Figure 9) and the transport of the densely coated 200 nm particles in CF sputum approached their theoretical speed in water. However, when NAC was used in combination with mucoadhesive cationic liposomes and polymers for gene therapy, there was no observable correction of nasal transepithelial potential difference in CF- mice [43].Figure 8.

Bottom Line: The mutation results in the accumulation of viscous mucus in multiple organs especially in the lungs, liver and pancreas.High associated morbidity and mortality is caused by CF due to the lack of effective therapies.Second, local lung delivery substantially prevents the penetration of the delivered drug into the systemic circulation limiting adverse side effects of the treatment on other organs and tissues.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey , Piscataway, NJ , USA.

ABSTRACT
Cystic fibrosis (CF) is an autosomal recessive monogenetic disease that afflicts nearly 70,000 patients worldwide. The mutation results in the accumulation of viscous mucus in multiple organs especially in the lungs, liver and pancreas. High associated morbidity and mortality is caused by CF due to the lack of effective therapies. It is widely accepted that morbidity and mortality caused by CF is primarily due to the respiratory manifestations of the disease. Consequently, several approaches were recently developed for treatment of lung complications of CF. However, the lack of effective methods for delivery and especially targeted delivery of therapeutics specifically to lung tissues and cells limits the efficiency of the therapy. Local pulmonary delivery of therapeutics has two major advantages over systemic application. First, it enhances the accumulation of therapeutics specifically in the lungs and therefore increases the efficiency of the treatment. Second, local lung delivery substantially prevents the penetration of the delivered drug into the systemic circulation limiting adverse side effects of the treatment on other organs and tissues. This review is focused on different approaches to the treatment of respiratory manifestations of CF as well as on methods of pulmonary delivery of therapeutics.

Show MeSH
Related in: MedlinePlus