Pulmonary delivery of therapeutic peptides and proteins

Adjei, Akwete; Gupta, Pramod

doi:10.1016/0168-3659(94)90081-7

Cited by 65 publications

(40 citation statements)

References 26 publications

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“…Efficient systemic absorption results from unique physiological features of the lung: the large absorptive surface area, the very thin diffusion path to the bloodstream, the elevated blood flow, the relatively low metabolic activity locally as well as the avoidance of first-pass hepatic metabolism. 6 Dry powder inhalers present advantages over nebulizers and metered-dose inhalers for the administration of peptide and protein therapeutics to the lung. Dry powder inhalers are portable, easy to operate (breath-actuated), inexpensive, propellant-free, and show improved stability of the formulation as a result of the dry state.…”

Section: Introductionmentioning

confidence: 99%

Systemic delivery of parathyroid hormone (1-34) using inhalation dry powders in rats

Codrons

Vanderbist

Verbeeck

et al. 2003

Journal of Pharmaceutical Sciences

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The aim of this work was to prepare and characterize inhalation dry powders of human parathyroid hormone (PTH), as well as to assess their efficacy for systemic delivery of the peptide and safety in rats. The powders were prepared by spray-drying using PTH, sugars, dipalmitoylphosphatidylcholine, and/or albumin. They presented an average primary particle diameter of 4.5 mm and tap density of 0.06 g/cm 3 , a mass median aerodynamic diameter between 3.9 and 5.9 mm, and reached up to 98% emitted dose and up to 61% fine particle fraction in the multi-stage liquid impinger using a Spinhaler inhaler device. Varying the airflow rate from 30 to 100 L/min had limited influence on the aerodynamic behavior of the aerosols. The absolute PTH bioavailability was 21% after intratracheal administration of the powder formed of PTH/albumin/ lactose/dipalmitoylphosphatidylcholine and 18% after subcutaneous injection in rats. Equilibrium dialysis revealed a 78% binding of PTH to albumin and the withdrawal of albumin from the powder increased absolute bioavailability after inhalation from 21 to 34%. No acute inflammation appeared in the lung up to 48 h after a single inhalation. The increased bioavailability of the optimized powder aerosol of PTH makes it a promising alternative to subcutaneous injection. ß

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Section: Introductionmentioning

confidence: 99%

Systemic delivery of parathyroid hormone (1-34) using inhalation dry powders in rats

Codrons

Vanderbist

Verbeeck

et al. 2003

Journal of Pharmaceutical Sciences

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“…AerX involves the delivery of a liquid drug solution through small plates into which laser-etched holds have been drilled (Schuster et al, 1997). The plates can be discarded after each use, permitting AerX to maintain solution sterility, a principal concern for liquid-based protein solutions (Adjei, 2000). Both systems produce insulin bioavailabilities in early human studies ranging from 10-13% (Brunner et al, 2001;Skyler et al, 2001), with bioavailability defined here as the percent area-under-the-curve (AUC) of exogenous systemic insulin by inhalation (as plotted vs. time) relative to the equivalent AUC obtained by subcutaneous insulin injection, with the dose adjusted.…”

Section: How Efficient Can Aerosol Therapy Be?mentioning

confidence: 99%

Delivery of biological agents by aerosols

Edwards

2002

AIChE Journal

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“…Successful alternatives must achieve acceptable bioavailability, reproducibility, safety, cost, and patient compliance. Inhalation delivery has attracted recent tremendous attention since a number of peptides or proteins are more efficiently absorbed from the lungs than via the oral, nasal, or transdermal routes [Adjei and Gupta, 1997;Wall, 1995;Sayani and Chien, 1996;Lee, 1992].…”

Section: Introductionmentioning

confidence: 99%