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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 PuffHaler®(Aktiv-Dry, LLC, Boulder, CO, USA) (A) and the Solovent®(Becton, Dickinson and Company, Franklin Lakes, NJ, USA) (B) are two new devices that are being developed to deliver measles vaccine as a dry powder to children and infants in developing countries. When the PuffHaler squeeze bulb is compressed, the silicone rubber burst-valve pops open. The air rushes into the disperser through the powder in an aluminum foil blister and the aerosol cloud fills a collapsed plastic bag reservoir. The aerosol-filled bag is detached and affixed to a facemask from which the subject breathes for 30 s to become vaccinated (Puff-mask). The syringe of the BD Solovent device is used to pressurize the capsule containing the powder vaccine. As the pressure rises, the thin films sealing the capsule rupture, and the powder is expelled and captured in the disposable spacer for delivery through a silicone facemask (Sol-mask) (from Reference [76] with Permission).
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Fig6: The PuffHaler®(Aktiv-Dry, LLC, Boulder, CO, USA) (A) and the Solovent®(Becton, Dickinson and Company, Franklin Lakes, NJ, USA) (B) are two new devices that are being developed to deliver measles vaccine as a dry powder to children and infants in developing countries. When the PuffHaler squeeze bulb is compressed, the silicone rubber burst-valve pops open. The air rushes into the disperser through the powder in an aluminum foil blister and the aerosol cloud fills a collapsed plastic bag reservoir. The aerosol-filled bag is detached and affixed to a facemask from which the subject breathes for 30 s to become vaccinated (Puff-mask). The syringe of the BD Solovent device is used to pressurize the capsule containing the powder vaccine. As the pressure rises, the thin films sealing the capsule rupture, and the powder is expelled and captured in the disposable spacer for delivery through a silicone facemask (Sol-mask) (from Reference [76] with Permission).

Mentions: Within the last 6–8 years, the WHO, the U.S. CDC, the Bill and Melinda Gates Foundation, the NIH and Aktiv-Dry, LLC (Boulder, CO, USA) began working on a powder formulation of the EZ live-attenuated measles vaccine. The advantage to a powder formulation is that it does not need refrigeration, which is also often lacking at sites of mass campaigns in developing countries. The powder was developed by Aktiv-Dry, LLC. The two devices to deliver the powder are called the PuffHaler® and the Solovent® and are shown in Figure 6A and 6B. They were developed by Aktiv-Dry and BD Technologies (Becton, Dickinson and Company), respectively. Both devices incorporate a holding chamber that allows the powder to be actuated and held in place until inhalation is initiated. Such a holding chamber for a powder aerosol was first introduced in the Exubera® Pulmonary Insulin Delivery System that was used to administer insulin aerosol. Unlike the Exubera device, these devices are constructed of inexpensive materials such that the cost of delivering dry powder measles vaccine will not cost more than intramuscular injection administration. Both devices also include flexible face masks for infant delivery. In a recent pre-clinical trial, dry powder vaccine delivered by these two devices provided full protection against measles infection in Rhesus macaques [76]. A large clinical trial to test the efficacy of this powder formulation in humans is currently being planned.Figure 6


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

Laube BL - Transl Respir Med (2014)

The PuffHaler®(Aktiv-Dry, LLC, Boulder, CO, USA) (A) and the Solovent®(Becton, Dickinson and Company, Franklin Lakes, NJ, USA) (B) are two new devices that are being developed to deliver measles vaccine as a dry powder to children and infants in developing countries. When the PuffHaler squeeze bulb is compressed, the silicone rubber burst-valve pops open. The air rushes into the disperser through the powder in an aluminum foil blister and the aerosol cloud fills a collapsed plastic bag reservoir. The aerosol-filled bag is detached and affixed to a facemask from which the subject breathes for 30 s to become vaccinated (Puff-mask). The syringe of the BD Solovent device is used to pressurize the capsule containing the powder vaccine. As the pressure rises, the thin films sealing the capsule rupture, and the powder is expelled and captured in the disposable spacer for delivery through a silicone facemask (Sol-mask) (from Reference [76] with Permission).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Fig6: The PuffHaler®(Aktiv-Dry, LLC, Boulder, CO, USA) (A) and the Solovent®(Becton, Dickinson and Company, Franklin Lakes, NJ, USA) (B) are two new devices that are being developed to deliver measles vaccine as a dry powder to children and infants in developing countries. When the PuffHaler squeeze bulb is compressed, the silicone rubber burst-valve pops open. The air rushes into the disperser through the powder in an aluminum foil blister and the aerosol cloud fills a collapsed plastic bag reservoir. The aerosol-filled bag is detached and affixed to a facemask from which the subject breathes for 30 s to become vaccinated (Puff-mask). The syringe of the BD Solovent device is used to pressurize the capsule containing the powder vaccine. As the pressure rises, the thin films sealing the capsule rupture, and the powder is expelled and captured in the disposable spacer for delivery through a silicone facemask (Sol-mask) (from Reference [76] with Permission).
Mentions: Within the last 6–8 years, the WHO, the U.S. CDC, the Bill and Melinda Gates Foundation, the NIH and Aktiv-Dry, LLC (Boulder, CO, USA) began working on a powder formulation of the EZ live-attenuated measles vaccine. The advantage to a powder formulation is that it does not need refrigeration, which is also often lacking at sites of mass campaigns in developing countries. The powder was developed by Aktiv-Dry, LLC. The two devices to deliver the powder are called the PuffHaler® and the Solovent® and are shown in Figure 6A and 6B. They were developed by Aktiv-Dry and BD Technologies (Becton, Dickinson and Company), respectively. Both devices incorporate a holding chamber that allows the powder to be actuated and held in place until inhalation is initiated. Such a holding chamber for a powder aerosol was first introduced in the Exubera® Pulmonary Insulin Delivery System that was used to administer insulin aerosol. Unlike the Exubera device, these devices are constructed of inexpensive materials such that the cost of delivering dry powder measles vaccine will not cost more than intramuscular injection administration. Both devices also include flexible face masks for infant delivery. In a recent pre-clinical trial, dry powder vaccine delivered by these two devices provided full protection against measles infection in Rhesus macaques [76]. A large clinical trial to test the efficacy of this powder formulation in humans is currently being planned.Figure 6

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