Development of small alginate microcapsules for recombinant gene product delivery to the rodent brain

Abstract

A novel form of gene therapy using encapsulated recombinant cells in alginate microcapsules has proven effective in treating several animal models of human diseases. For treating neurological deficits in rodents with this technology, the size of the microcapsules has to be reduced for implantation in the central nervous system (CNS) to bypass the blood–brain barrier. This article reports the development of small alginate microcapsules suitable for implantation into the mouse CNS. By varying the encapsulation protocol, recombinant cells could be encapsulated in microcapsules ranging in diameter from 5 to 2000 μm. The optimal size for implantation was determined to be 100–200 μm, based on the smallest, homogeneously sized, cell-filled microcapsules that could pass the 500 μm inner diameter of a CNS-implantation needle. Compared with medium-sized (500–700 μm) microcapsules, these small microcapsules packed more tightly together with less inter-capsule space, resulting in an increased number of cells and a higher rate of recombinant gene product secretion per volume of microcapsules. The small microcapsules also displayed increased mechanical strength, compared with large microcapsules. These excellent in vitro properties of small 100–200 μm microcapsules warrant further in vivo investigation into the feasibility of using immuno-isolation gene therapy to deliver recombinant gene products to the rodent CNS.