Amorphous Calcium Carbonate Based-Microparticles for Peptide Pulmonary Delivery

• Published in: ACS applied materials & interfaces Vol. 8; no. 2; pp. 1164 - 1175
• Main Authors: Tewes, Frederic, Gobbo, Oliviero L, Ehrhardt, Carsten, Healy, Anne Marie
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 20-01-2016; Washington, D.C. : American Chemical Society
• Subjects: Administration, Inhalation; Aerosols - chemistry; Aerosols - therapeutic use; alpha 1-Antitrypsin - administration & dosage; alpha 1-Antitrypsin - chemistry; Animals; Calcitonin - administration & dosage; Calcitonin - chemistry; Calcium Carbonate - administration & dosage; Calcium Carbonate - chemistry; Humans; Life Sciences; Lung Diseases - drug therapy; Lung Diseases - pathology; Nanoparticles - administration & dosage; Nanoparticles - chemistry; Particle Size; Peptides - administration & dosage; Peptides - chemistry; Pharmaceutical sciences; Rats; biomimetic process; peptide; amorphous calcium carbonate; pulmonary inhalation; composite microparticle
• ISSN: 1944-8244; 1944-8252
• DOI: 10.1021/acsami.5b09023

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.