Sustained delivery of immunoglobulins from polymer microsources on a narrow surface of the developing rat brain

Abstract

Studies of postnatal neurogenesis have benefited from the use of a relatively non-invasive method for chronic delivery of bioactive substances to a restricted area of cortex. This method consists of the implantation of an Elvax polymer microsource of active substances close to the targeted brain surface. Receptor ligands, as well as macromolecules such as proteins, peptides and enzymes have been shown to be released by the implants in a sustained manner over weeks. Here we describe the kinetics and immunoreactivity of different immunoglobulins released in vitro and in vivo by Elvax polymer. In vitro, the immunoglobulins first diffuse during a burst phase from the pore network of the polymer matrix. Release continues during a slow phase depending on loading, porosity and volume of the matrix but also on intrinsic properties of immunoglobulins. Elvax microsources loaded either with anti-TAG-1 or with anti-HNK-1 antibodies according to the release data in vitro, are implanted on the posterior cerebellar cortex of postnatal rats during the period when the targeted antigens are expressed by the differentiating cells. After several days, the released immunoreactive antibodies are located at the antigenic sites within the cerebellar cortex close to the implants. The sustained local delivery of immunoglobulins using the Elvax implant method allows access to cell surface and matrix molecules and thereby to the mechanisms they control during postnatal neurogenesis.