title: Amorphous Calcium Carbonate Based-Microparticles for Peptide Pulmonary Delivery.
abstract: Amorphous calcium carbonate (ACC) is known to interact with proteins, for example, in biogenic ACC, to form stable amorphous phases. The control of amorphous/crystalline and inorganic/organic ratios in inhalable calcium carbonate microparticles may enable particle properties to be adapted to suit the requirements of dry powders for pulmonary delivery by oral inhalation. For example, an amorphous phase can immobilize and stabilize polypeptides in their native structure and amorphous and crystalline phases have different mechanical properties. Therefore, inhalable composite microparticles made of inorganic (i.e., calcium carbonate and calcium formate) and organic (i.e., hyaluronan (HA)) amorphous and crystalline phases were investigated for peptide and protein pulmonary aerosol delivery. The crystalline/amorphous ratio and polymorphic form of the inorganic component was altered by changing the microparticle drying rate and by changing the ammonium carbonate and HA initial concentration. The bioactivity of the model peptide, salmon calcitonin (sCT), coprocessed with alpha-1-antitrypsin (AAT), a model protein with peptidase inhibitor activity, was maintained during processing and the microparticles had excellent aerodynamic properties, making them suitable for pulmonary aerosol delivery. The bioavailability of sCT after aerosol delivery as sCT and AAT-loaded composite microparticles to rats was 4-times higher than that of sCT solution.
authors.affiliation: School of Pharmacy and Pharmaceutical Sciences, Trinity College Dublin , Dublin 2, Ireland.|INSERM U 1070, Pôle Biologie-Santé, Université de Poitiers , Faculté de Médecine & Pharmacie, 1 Rue Georges Bonnet, 86022 Poitiers Cedex, France.
authors.forename: Frederic
authors.initials: F
authors.lastname: Tewes
authors.affiliation: School of Pharmacy and Pharmaceutical Sciences, Trinity College Dublin , Dublin 2, Ireland.
authors.forename: Oliviero L
authors.initials: OL
authors.lastname: Gobbo
authors.affiliation: School of Pharmacy and Pharmaceutical Sciences, Trinity College Dublin , Dublin 2, Ireland.
authors.forename: Carsten
authors.initials: C
authors.lastname: Ehrhardt
authors.affiliation: School of Pharmacy and Pharmaceutical Sciences, Trinity College Dublin , Dublin 2, Ireland.
authors.forename: Anne Marie
authors.initials: AM
authors.lastname: Healy
mesh_terms: D000280:Administration, Inhalation; D000336:Aerosols / Q000737:chemistry / Q000627:therapeutic use; D000818:Animals; D002116:Calcitonin / Q000008:administration & dosage / Q000737:chemistry; D002119:Calcium Carbonate / Q000008:administration & dosage / Q000737:chemistry*; D006801:Humans; D008171:Lung Diseases / Q000188:drug therapy* / Q000473:pathology; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry*; D010316:Particle Size; D010455:Peptides / Q000008:administration & dosage / Q000737:chemistry*; D051381:Rats; D000515:alpha 1-Antitrypsin / Q000008:administration & dosage / Q000737:chemistry
chemical_list: D000336:Aerosols; D010455:Peptides; C043392:SERPINA1 protein, human; D000515:alpha 1-Antitrypsin; C028815:salmon calcitonin; D002116:Calcitonin; D002119:Calcium Carbonate
keywords: amorphous calcium carbonate; biomimetic process; composite microparticle; peptide; pulmonary inhalation