Intratracheal Delivery of Peptide and Protein Agents: Absorption from Solution and Dry Powder by Rat Lung †

Komada, Fusao; Iwakawa, Seigo; Yamamoto, Nakayuki; Sakakibara, H.; Okumura, Katsuhiko

doi:10.1002/jps.2600830621

Cited by 66 publications

(29 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As a technique for delivering drugs to the lung, dry powder inhalation is considered one of the most promising [1][2][3][4][5][6] due to its many advantages, such as (1) absence of the need for propellants such as chlorofluorocarbon, (2) portability, and (3) relatively low cost. 7,8) For inhalation of a drug powder into the lungs and its deposition, efficiently dispersed drugs with an aerodynamic diameter of 1.0-6.0 mm are most effective for the delivery of particles.…”

mentioning

confidence: 99%

Preparation of Dry Powder Inhalation by Surface Treatment of Lactose Carrier Particles.

et al. 2003

View full text Add to dashboard Cite

An attempt was made to produce carrier particles for dry powder inhalations by the surface treatment of lactose particles with aqueous ethanol solution. Drug/carrier powder mixtures were prepared consisting of lactose carriers with different particle surface properties and micronized salbutamol sulfate. These powder mixtures were aerosolized by Spinhaler ® , and in vitro deposition properties of salbutamol sulfate were evaluated by twin impinger. The degree of adhesion between drug particles and carrier particles was determined by the ultracentrifuge separation method. In addition, the air jet sieve method was used to evaluate characteristics of the separation of drug particles from carrier particles in airflow. The average adhesion force (F50) between the surface-treated lactose carrier and drug particles was significantly lower than that of powder mixed with the untreated lactose carrier, indicating that the degree of separation (T50) of drug particles from carrier particles was improved when surface-treated lactose carrier was used. This resulted in an improvement of in vitro inhalation properties.

show abstract

mentioning

confidence: 99%

Preparation of Dry Powder Inhalation by Surface Treatment of Lactose Carrier Particles.

et al. 2003

View full text Add to dashboard Cite

show abstract

“…However, pulmonary delivery of major biotherapeutic products having larger molecular weights has not been successful. This is not unexpected, because many studies have demonstrated an inverse correlation between molecular size and the rate of clearance from the lung, i.e., absorption into the bloodstream (15,16). Our approach to delivery of large proteins such as Epo through the epithelial barrier in the lung was, therefore, to exploit an active carrier system, the FcRn pathway.…”

mentioning

confidence: 99%

Pulmonary delivery of an erythropoietin Fc fusion protein in non-human primates through an immunoglobulin transport pathway

Bitonti

Dumont

Low

et al. 2004

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

210

179

View full text Add to dashboard Cite

Administration of therapeutic proteins by methods other than injection is limited, in part, by inefficient penetration of epithelial barriers. Therefore, unique approaches to breaching these barriers are needed. The neonatal constant region fragment (Fc) receptor (FcRn), which is responsible for IgG transport across the intestinal epithelium in newborn rodents, is expressed in epithelial cells in adult humans and non-human primates. Here we show that FcRnmediated transport is functional in the lung of non-human primates and that this transport system can be used to deliver erythropoietin (Epo) when it is conjugated to the Fc domain of IgG1. FcRn-dependent absorption was more efficient when the EpoFc fusion protein was deposited predominantly in the upper and central airways of the lung, where epithelial expression of FcRn was most prominently detected. To optimize fusion protein absorption in the lung, we created a recombinant ''monomericEpo'' Fc fusion protein comprised of a single molecule of Epo conjugated to a dimeric Fc. This fusion protein exhibited enhanced pharmacokinetic and pharmacodynamic properties. The bioavailability of the EpoFc monomer when delivered through the lung was approximately equal to that reported for unconjugated Epo delivered s.c. in humans. These studies show that FcRn can be harnessed to noninvasively deliver bioactive proteins into the systemic circulation in therapeutic quantities.

show abstract

“…Okumara et al [1992] reached 13% relative bioavailability following instillation of an insulin solution, but 37-98% relative bioavailabilities using a metered-dose inhaler due to greater deposition in the peripheral zone of the lung. Komada et al [1994] administered a dry powder of insulin to rat lungs and achieved lower efficacy in systemic absorption, i.e., 6.5% absolute bioavailability. Edwards et al [1997] obtained 87.5% bioavailability following inhalation of large porous polylactic-coglycolic acid (PLGA) particles of insulin, as compared to the subcutaneous injection of identical particles.…”

Section: Discussionmentioning

confidence: 98%

Sustained release of insulin from insoluble inhaled particles

et al. 1999

View full text Add to dashboard Cite

Intratracheal Delivery of Peptide and Protein Agents: Absorption from Solution and Dry Powder by Rat Lung †

Cited by 66 publications

References 23 publications

Preparation of Dry Powder Inhalation by Surface Treatment of Lactose Carrier Particles.

Preparation of Dry Powder Inhalation by Surface Treatment of Lactose Carrier Particles.

Pulmonary delivery of an erythropoietin Fc fusion protein in non-human primates through an immunoglobulin transport pathway

Sustained release of insulin from insoluble inhaled particles

Contact Info

Product

Resources

About