Encapsulation of a glycosaminoglycan in hydroxyapatite/alginate capsules

The development of suitable vehicles for the delivery of growth-inducing factors to fracture sites is a challenging area of bone repair. Bone-specific glycosaminoglycan molecules are of particular interest because of their high stability and proven effect on bone growth. Calcium alginate capsules are popular as delivery vehicles because of their low immunogenic response; they offer a versatile route that enables the controlled release of heparin (a member of the glycosaminoglycan family). In this study, hydroxyapatite (HA)/alginate composite capsules are explored as novel drug delivery vehicles for heparin, using both medium- and low-viscosity alginates. The composition, structure, and stability of the capsules are fully characterized and correlated to the release of heparin in vitro. Heparin is found to associate both with the alginate matrix through polymeric flocculation and also with the HA crystals in the composite beads. The mechanism by which heparin is released is dictated by the stability of the capsule in a particular release media and by the composition of the capsule. The use of medium-viscosity alginate is advantageous with respect to both drug loading and prolonging the release. The inclusion of HA increases the encapsulation efficiency, but because of its destabilizing effect to the alginate hydrogel matrix, it also increases the rate of heparin release. The bioactivity of heparin is fully retained throughout the assembly and release processes. (C) 2008 Wiley Periodicals, Inc. J Biomed Mater Res 91A: 866-877, 2009