Protein–polysaccharide complexes for enhanced protein delivery in hyaluronic acid templated calcium carbonate microparticles

Abstract

International audienceThe controlled delivery of proteins within calcium carbonate (CaCO 3) particles is currently widely investigated. The success of these carriers is driven by ionic interactions between the encapsulated proteins and the particles. This poses a great limitation on the successful loading of proteins that have no ionic affinity to CaCO 3. In this study, we explored the use of polysaccharide–protein interactions to strongly enhance the encapsulation of proteins in CaCO 3 microparticles. Previously, Vandevenne and colleagues inserted a human chitin binding domain (ChBD) that has intrinsic affinity for hyaluronic acid (HA) into a b-lactamase (BlaP). This generated chimeric protein, named BlaPChBD, was shown to be fully bifunctional. In this study we showed that this hybrid protein can associate with HA and be successfully loaded into vaterite CaCO 3 microparticles using supercritical CO 2 (ScCO 2) technology aided by the templating effect of HA on CaCO 3. The presence of ChBD inserted into BlaP increased the encapsulation of the protein by 6-fold when complexed with HA. Furthermore, thrombin cleavage sites were engineered on both sides of the inserted ChBD in the chimeric BlaP to achieve release of the protein from the micro-particles by protease cleavage. Our results showed that thrombin cleavage increased the release of the protein from the microparticles within 36 hours from o20% to 87%. In conclusion, the presence of ChBD successfully improved the encapsulation yield of the protein while retaining up to 82% of its activity and efficient release of the protein from the microparticles was achieved by protease cleavage

Phase-specific bioactivity and altered Ostwald ripening pathways of calcium carbonate polymorphs in simulated body fluid

“…6 Subsequently, it was shown that aragonite is bioresorbable and that aragonite and other calcium carbonate polymorphs can serve as a drug release system. [7][8][9][10][11][12][13] Despite the widespread occurrence of calcium carbonate in the biosphere, e.g., in human otoliths, it seems that the full potential of the calcium carbonate system is not yet tapped for the purposeful design of bioactive and bioresorbable biomaterials/ bioceramics. Recent research also rose our awareness that calcium carbonate formation contributes to the bioactivity of bioglass.…”

Hyaluronic-Acid-Based Organic-Inorganic Composites for Biomedical Applications

“…The high protein entrapment efficiency of CaCO 3 particles was reported in [ 130 ]. The interactions of proteins with CaCO 3 particles were investigated [ 131 ] and used for the development of HYH-based composites containing CaCO 3 particles loaded with proteins for controlled protein release.…”

CaCO3 vaterites as components of target drug delivery systems

“…Aft er dissolution of CaCO 3 cores in the presence of chelate compounds (e.g., ethylenediaminetetraacetic acid), these multilayered shells were used as capsules for delivery of biologically active compounds [2]. In some cases, carbonate cores were not dissolved, but used together with their PE shells [3][4][5]. Since one of the objectives of employing delivery systems is to provide prolonged release of an encapsulated MC, preservation of the porous core increases resistance of the structure against external infl uence and thus helps attain this goal.…”