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Amorphous Calcium Carbonate Based-Microparticles for Peptide Pulmonary Delivery
Frederic Tewes1,2, Oliviero L Gobbo1, Carsten Ehrhardt1
1School of Pharmacy and Pharmaceutical Sciences, Trinity College Dublin , Dublin 2, Ireland.
ACS Applied Materials & Interfaces
|December 23, 2015
Summary
Researchers developed inhalable composite microparticles using amorphous calcium carbonate (ACC) and hyaluronan (HA) for drug delivery. These particles enhance peptide and protein stability and bioavailability for pulmonary administration.
Area of Science:
- Materials Science
- Biotechnology
- Pharmaceutical Sciences
Background:
- Amorphous calcium carbonate (ACC) interacts with proteins, forming stable amorphous phases relevant for biogenic materials.
- Controlling amorphous/crystalline and inorganic/organic ratios in microparticles is key for optimizing dry powder inhaler formulations.
- Amorphous phases can stabilize native protein structures, while different phases affect mechanical properties crucial for pulmonary delivery.
Purpose of the Study:
- To investigate inhalable composite microparticles for peptide and protein pulmonary aerosol delivery.
- To explore the use of inorganic (calcium carbonate, calcium formate) and organic (hyaluronan) phases in microparticle formulation.
- To assess the impact of varying crystalline/amorphous ratios and polymorphic forms on particle properties and drug delivery.
Main Methods:
- Fabrication of inhalable composite microparticles using calcium carbonate, calcium formate, and hyaluronan.
- Manipulation of crystalline/amorphous ratios and inorganic/organic content by altering drying rates and initial concentrations.
- Evaluation of microparticle aerodynamic properties for pulmonary aerosol delivery.
- Assessment of model peptide (salmon calcitonin) and protein (alpha-1-antitrypsin) bioactivity and stability.
Main Results:
- Composite microparticles exhibited suitable aerodynamic properties for pulmonary delivery.
- The bioactivity of salmon calcitonin (sCT) and alpha-1-antitrypsin (AAT) was preserved during processing.
- A four-fold increase in sCT bioavailability was observed after aerosol delivery using the composite microparticles compared to a solution.
Conclusions:
- Inhalable composite microparticles offer a promising platform for pulmonary drug delivery of peptides and proteins.
- Controlling the inorganic/organic and amorphous/crystalline composition allows for tailored particle properties.
- This approach significantly enhances the bioavailability of drugs delivered via oral inhalation.
