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The expanding role of aerosols in systemic drug delivery, gene therapy and vaccination: an update.

Laube BL - Transl Respir Med (2014)

Bottom Line: The early promise of aerosolized systemic drug delivery and its outlook for future success will be highlighted.Finally, progress in the development of aerosolized vaccination will be presented.The continued expansion of the role of aerosol therapy in the future will depend on: (1) improving the bioavailability of systemically delivered drugs; (2) developing gene therapy vectors that can efficiently penetrate the mucus barrier and cell membrane, navigate the cell cytoplasm and efficiently transfer DNA material to the cell nucleus; (3) improving delivery of gene vectors and vaccines to infants; and (4) developing formulations that are safe for acute and chronic administrations.

View Article: PubMed Central - PubMed

Affiliation: The Johns Hopkins Medical Institutions, Suite 3015, The David M. Rubenstein Building, 200 North Wolfe Street, Baltimore, MD 21287 USA.

ABSTRACT
Until the late 1990s, aerosol therapy consisted of beta2-adrenergic agonists, anti-cholinergics, steroidal and non-steroidal agents, mucolytics and antibiotics that were used to treat patients with asthma, COPD and cystic fibrosis. Since then, inhalation therapy has matured to include drugs that: (1) are designed to treat diseases outside the lung and whose target is the systemic circulation (systemic drug delivery); (2) deliver nucleic acids that lead to permanent expression of a gene construct, or protein coding sequence, in a population of cells (gene therapy); and (3) provide needle-free immunization against disease (aerosolized vaccination). During the evolution of these advanced applications, it was also necessary to develop new devices that provided increased dosing efficiency and less loss during delivery. This review will present an update on the success of each of these new applications and their devices. The early promise of aerosolized systemic drug delivery and its outlook for future success will be highlighted. In addition, the challenges to aerosolized gene therapy and the need for appropriate gene vectors will be discussed. Finally, progress in the development of aerosolized vaccination will be presented. The continued expansion of the role of aerosol therapy in the future will depend on: (1) improving the bioavailability of systemically delivered drugs; (2) developing gene therapy vectors that can efficiently penetrate the mucus barrier and cell membrane, navigate the cell cytoplasm and efficiently transfer DNA material to the cell nucleus; (3) improving delivery of gene vectors and vaccines to infants; and (4) developing formulations that are safe for acute and chronic administrations.

No MeSH data available.


Related in: MedlinePlus

Percent of people with cystic fibrosis by age with normal/mild forced expiratory volume in one second (FEV1), moderate FEV1and severe FEV1. The majority of children have FEV1 values in the normal to mild range, indicating mild disease and mild airway obstruction. Adults age 18–29 and 30+ have FEV1 values in the moderate to severe range, indicating severe disease and increased airway obstruction (downloaded from Cystic Fibrosis Foundation website at http://www.cff.org/UploadedFiles/Research/ClinicalResearch/2011-Patient-Registry.pdf).
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Fig3: Percent of people with cystic fibrosis by age with normal/mild forced expiratory volume in one second (FEV1), moderate FEV1and severe FEV1. The majority of children have FEV1 values in the normal to mild range, indicating mild disease and mild airway obstruction. Adults age 18–29 and 30+ have FEV1 values in the moderate to severe range, indicating severe disease and increased airway obstruction (downloaded from Cystic Fibrosis Foundation website at http://www.cff.org/UploadedFiles/Research/ClinicalResearch/2011-Patient-Registry.pdf).

Mentions: Another challenge has been uniform delivery of the drug vector to the lungs of adult patients with CF. Disease in adults with CF is significantly more severe, compared to children with CF (Figure 3) [49]. Increased disease severity is shown by a lower percent forced expiratory volume in one second (FEV1) in adults, compared to children. Increased severity in disease leads to uneven distribution of the drug vector, with areas of the lung that are unobstructed receiving a higher dose of vector than regions that are partially, or fully obstructed (Figure 4). Such uneven distribution of the drug vector could make treatment less efficacious. These same challenges are likely to apply to treating infants, or adults with obstructed airways, with aerosolized gene vectors for other lung diseases.Figure 3


The expanding role of aerosols in systemic drug delivery, gene therapy and vaccination: an update.

Laube BL - Transl Respir Med (2014)

Percent of people with cystic fibrosis by age with normal/mild forced expiratory volume in one second (FEV1), moderate FEV1and severe FEV1. The majority of children have FEV1 values in the normal to mild range, indicating mild disease and mild airway obstruction. Adults age 18–29 and 30+ have FEV1 values in the moderate to severe range, indicating severe disease and increased airway obstruction (downloaded from Cystic Fibrosis Foundation website at http://www.cff.org/UploadedFiles/Research/ClinicalResearch/2011-Patient-Registry.pdf).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4215822&req=5

Fig3: Percent of people with cystic fibrosis by age with normal/mild forced expiratory volume in one second (FEV1), moderate FEV1and severe FEV1. The majority of children have FEV1 values in the normal to mild range, indicating mild disease and mild airway obstruction. Adults age 18–29 and 30+ have FEV1 values in the moderate to severe range, indicating severe disease and increased airway obstruction (downloaded from Cystic Fibrosis Foundation website at http://www.cff.org/UploadedFiles/Research/ClinicalResearch/2011-Patient-Registry.pdf).
Mentions: Another challenge has been uniform delivery of the drug vector to the lungs of adult patients with CF. Disease in adults with CF is significantly more severe, compared to children with CF (Figure 3) [49]. Increased disease severity is shown by a lower percent forced expiratory volume in one second (FEV1) in adults, compared to children. Increased severity in disease leads to uneven distribution of the drug vector, with areas of the lung that are unobstructed receiving a higher dose of vector than regions that are partially, or fully obstructed (Figure 4). Such uneven distribution of the drug vector could make treatment less efficacious. These same challenges are likely to apply to treating infants, or adults with obstructed airways, with aerosolized gene vectors for other lung diseases.Figure 3

Bottom Line: The early promise of aerosolized systemic drug delivery and its outlook for future success will be highlighted.Finally, progress in the development of aerosolized vaccination will be presented.The continued expansion of the role of aerosol therapy in the future will depend on: (1) improving the bioavailability of systemically delivered drugs; (2) developing gene therapy vectors that can efficiently penetrate the mucus barrier and cell membrane, navigate the cell cytoplasm and efficiently transfer DNA material to the cell nucleus; (3) improving delivery of gene vectors and vaccines to infants; and (4) developing formulations that are safe for acute and chronic administrations.

View Article: PubMed Central - PubMed

Affiliation: The Johns Hopkins Medical Institutions, Suite 3015, The David M. Rubenstein Building, 200 North Wolfe Street, Baltimore, MD 21287 USA.

ABSTRACT
Until the late 1990s, aerosol therapy consisted of beta2-adrenergic agonists, anti-cholinergics, steroidal and non-steroidal agents, mucolytics and antibiotics that were used to treat patients with asthma, COPD and cystic fibrosis. Since then, inhalation therapy has matured to include drugs that: (1) are designed to treat diseases outside the lung and whose target is the systemic circulation (systemic drug delivery); (2) deliver nucleic acids that lead to permanent expression of a gene construct, or protein coding sequence, in a population of cells (gene therapy); and (3) provide needle-free immunization against disease (aerosolized vaccination). During the evolution of these advanced applications, it was also necessary to develop new devices that provided increased dosing efficiency and less loss during delivery. This review will present an update on the success of each of these new applications and their devices. The early promise of aerosolized systemic drug delivery and its outlook for future success will be highlighted. In addition, the challenges to aerosolized gene therapy and the need for appropriate gene vectors will be discussed. Finally, progress in the development of aerosolized vaccination will be presented. The continued expansion of the role of aerosol therapy in the future will depend on: (1) improving the bioavailability of systemically delivered drugs; (2) developing gene therapy vectors that can efficiently penetrate the mucus barrier and cell membrane, navigate the cell cytoplasm and efficiently transfer DNA material to the cell nucleus; (3) improving delivery of gene vectors and vaccines to infants; and (4) developing formulations that are safe for acute and chronic administrations.

No MeSH data available.


Related in: MedlinePlus