4.8 Article

Stability and cell uptake of calcium carbonate templated insulin microparticles

Journal

ACTA BIOMATERIALIA
Volume 10, Issue 3, Pages 1423-1430

Publisher

ELSEVIER SCI LTD
DOI: 10.1016/j.actbio.2013.11.011

Keywords

Microparticles; Micromechanics; Biopharmaceuticals; Hard templating; Microgels

Funding

  1. Alexander von Humboldt Foundation

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Therapeutic proteins are an integral part of today's pharmaceutical practice, but they still present challenges from the drug delivery point of view. In this work, a new approach is studied based on hard ternplating for fabrication of microparticles composed of pure insulin, which may enable effective delivery, for instance pulmonary delivery. The approach is both simple and versatile: the protein particles are prepared by selective precipitation into porous CaCO3 microtemplates, followed by full decomposition of the template at the isoelectric point of the protein (pH 5.2). Control over the main material parameters (mechanical properties, porosity, morphology and stability at physiological conditions) are critical for the envisioned application in drug delivery. It is demonstrated that these critical parameters can be significantly tuned by a slight final pH variation around the isoelectric point (pH range 4-6) and by the denaturation degree of insulin. Electrostatic interactions and inter-protein crosslinking in the protein particles as well as their internal structure are considered, to explain the variation in the particle properties. The particle property parameters are explored using atomic force microscopy, optical microscopy and circular dichroism spectra. Finally, phagocytic clearance of the protein particles in vitro was studied to explore possible enhancements in particle fabrication to improve the efficiency of insulin delivery by inhalation. (C) 2013 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

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