Control of physicochemical and cargo release properties of cross-linked alginate microcapsules formed by spray-drying

Encapsulation in dry cross-linked alginate microbeads has numerous applications in pharmaceutics, food, and agriculture. Recently, we developed an innovative, industrially scalable, and cost-effective method in which alginates are cross-linked in-situ during spray-drying to form cross-linked alginate microcapsules (CLAMs), consolidating a series of unit operations into a single step. This study investigated the control of alginate matrix cross-linking by modulating the CaHPO4 content and explored the subsequent impact on CLAM physicochemical properties. Maximum cross-linking was achieved at CaHPO4 feed contents greater than 0.2% (w/w). CLAMs prepared with >= 0.25% CaHPO4 in the spray-dryer inlet feed contained residual insoluble CaHPO4, and particle morphology of such CLAMs tended to appear more spherical and less dramatically collapsed than less crosslinked CLAMs. Cross-linking of CLAMs did not influence particle size. The release of dextran from CLAMs was examined in the context of matrix hydration and the dissociation of non cross-linked alginate from the matrix. Dextran release was characterized by a brief delay, followed by rapid release, concluding within 2 h. Elevated cross-linking slightly hindered the early release of FITC-labeled dextran from CLAMs. Alginate dissociation was delayed and less extensive in highly cross-linked CLAMs, suggesting alginate dissociation may govern the early stage of cargo release.