par Depreter, Flore ;Pilcer, Gabrielle ;Amighi, Karim
Référence International journal of pharmaceutics, 447, 1-2, page (251-280)
Publication Publié, 2013-04-15
Article révisé par les pairs
Résumé : Due to recent developments in biochemical engineering and in the understanding of the physiopathology of many diseases, therapeutic biologics are expected to become of increasing importance. Pulmonary delivery of these proteins could constitute an attractive, non-invasive alternative to parenteral delivery. It can be considered for either topical use for treating lung diseases or for systemic use for treating a variety of other diseases. However, administration of proteins to the lungs presents several challenges such as the need for appropriate formulation strategies to overcome high inter-particle interactions and physico-chemical degradation that can lead to loss of biological activity and/or safety issues. In addition, various lung clearance mechanisms have to be avoided to provide a sufficient level of intact protein in the lungs. If systemic action is desired, it is also necessary for the molecule to cross the alveolar epithelium, which is particularly challenging for large proteins with many hydrophilic domains.The purpose of this article is to review the main challenges in the formulation of proteins for inhalation and the possible strategies that can be applied. Because of the particular success of dry formulations in stabilising proteins, there is a special focus on their development, along with the drying techniques and stabilising excipients used. Finally, an overview is given of the existing commercial preparations and of the main clinical developments in inhaled proteins for either topical or systemic applications.