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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

The Aerogen Aeroneb Go®delivery system (Aerogen, Galway Ireland) is being developed to deliver liquid measles vaccine to children and infants in developing countries. The device consists of a medication chamber that is located in the upper part of a plastic holder. The outlet port extends from the holder and can be fitted with a mouthpiece or facemask. A vibrating membrane, the generator OnQ®, pumps fluid through small holes generating aerosol with a median diameter of 3.6 microns. The control module works with three AA batteries and is connected to the medication chamber through a removable cord [75]. (Image downloaded from Aerogen website at http:www.aerogen.com/aeroneb-go.html).
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Fig5: The Aerogen Aeroneb Go®delivery system (Aerogen, Galway Ireland) is being developed to deliver liquid measles vaccine to children and infants in developing countries. The device consists of a medication chamber that is located in the upper part of a plastic holder. The outlet port extends from the holder and can be fitted with a mouthpiece or facemask. A vibrating membrane, the generator OnQ®, pumps fluid through small holes generating aerosol with a median diameter of 3.6 microns. The control module works with three AA batteries and is connected to the medication chamber through a removable cord [75]. (Image downloaded from Aerogen website at http:www.aerogen.com/aeroneb-go.html).

Mentions: In the early 2000s, the World Health Organization (WHO) began work on an aerosolized measles vaccine that could be used in mass immunization campaigns in developing countries. The WHO decided to aerosolize the liquid formulation that was licensed for injection therapy and had proven effective by inhalation in earlier studies in Mexico [70, 71]. This was the Edmonston-Zagreb (EZ) live-attenuated measles vaccine. This choice meant that the WHO did not have to reformulate the vaccine, which could have resulted in years of additional testing. After several years of device development in collaboration with the U.S. CDC, the Bill and Melinda Gates Foundation and Aerogen (Galway, Ireland), the WHO began testing the Aerogen AeronebGo® delivery system in India. This is a portable, battery-operated vibrating mesh device with a face mask for infant aerosol delivery (Figure 5). A Phase III trial in 2,000 children <12 months old was recently completed. Data are being analyzed and results will be compared to those obtained with subcutaneous (SC) administration of measles vaccine in a similar age-group.Figure 5


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

Laube BL - Transl Respir Med (2014)

The Aerogen Aeroneb Go®delivery system (Aerogen, Galway Ireland) is being developed to deliver liquid measles vaccine to children and infants in developing countries. The device consists of a medication chamber that is located in the upper part of a plastic holder. The outlet port extends from the holder and can be fitted with a mouthpiece or facemask. A vibrating membrane, the generator OnQ®, pumps fluid through small holes generating aerosol with a median diameter of 3.6 microns. The control module works with three AA batteries and is connected to the medication chamber through a removable cord [75]. (Image downloaded from Aerogen website at http:www.aerogen.com/aeroneb-go.html).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Fig5: The Aerogen Aeroneb Go®delivery system (Aerogen, Galway Ireland) is being developed to deliver liquid measles vaccine to children and infants in developing countries. The device consists of a medication chamber that is located in the upper part of a plastic holder. The outlet port extends from the holder and can be fitted with a mouthpiece or facemask. A vibrating membrane, the generator OnQ®, pumps fluid through small holes generating aerosol with a median diameter of 3.6 microns. The control module works with three AA batteries and is connected to the medication chamber through a removable cord [75]. (Image downloaded from Aerogen website at http:www.aerogen.com/aeroneb-go.html).
Mentions: In the early 2000s, the World Health Organization (WHO) began work on an aerosolized measles vaccine that could be used in mass immunization campaigns in developing countries. The WHO decided to aerosolize the liquid formulation that was licensed for injection therapy and had proven effective by inhalation in earlier studies in Mexico [70, 71]. This was the Edmonston-Zagreb (EZ) live-attenuated measles vaccine. This choice meant that the WHO did not have to reformulate the vaccine, which could have resulted in years of additional testing. After several years of device development in collaboration with the U.S. CDC, the Bill and Melinda Gates Foundation and Aerogen (Galway, Ireland), the WHO began testing the Aerogen AeronebGo® delivery system in India. This is a portable, battery-operated vibrating mesh device with a face mask for infant aerosol delivery (Figure 5). A Phase III trial in 2,000 children <12 months old was recently completed. Data are being analyzed and results will be compared to those obtained with subcutaneous (SC) administration of measles vaccine in a similar age-group.Figure 5

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