No abstract

The purpose of this research effort was to evaluate in vivo a newly developed dexamethasone/PLGA microsphere system designed to suppress the inflammatory tissue response to an implanted device, in this case a biosensor. The microspheres were prepared using an oil/water (O/W) emulsion technique. The microsphere system was composed of drug-loaded microspheres (including newly formulated and predegraded microspheres) and free dexamethasone. The combination of the drug and drug-loaded microspheres provided burst release of dexamethasone followed by continuous release from days 2-14. Continuous release to at least 30 days was achieved by mixing predegraded and newly formulated microspheres. The ability of our mixed microsphere system to control tissue reactions to an implant then was tested in vivo using cotton thread sutures to induce inflammation subcutaneously in Sprague-Dawley rats. Two different in vivo studies were performed, the first to find the dosage level of dexamethasone that effectively would suppress the acute inflammatory reaction and the second to show how effective the dexamethasone delivered by PLGA microspheres was in suppressing chronic inflammatory response to an implant. The first in vivo study showed that 0.1 to 0.8 mg of dexamethasone at the site minimized the acute inflammatory reaction. The second in vivo study showed that our mixed microsphere system suppressed the inflammatory response to an implanted suture for at least 1 month. This study has proven the viability of microsphere delivery of an anti-inflammatory to control the inflammatory reaction at an implant site.

Multilayered films of humic acids (HAs) (naturally occurring biopolymers) were investigated as a potential semipermeable membrane for implantable glucose sensors. These films were grown using a layer-by-layer self-assembly process of HAs and oppositely charged ferric ions. The growth of these assemblies exhibited strong dependence on the pH and ionic strength of HAs solutions, which correlated with the degree of ionization of the carboxyl groups and neutralization-induced surface spreading. Quartz crystal microbalance (QCM) and ellipsometric studies have shown repeatable, stepwise increase in mass (as high as 5.63 microg/cm(2)) and in film thickness (ca. 24.3 nm per layer) for these assemblies. The permeability of glucose through these membranes can be regulated by varying the number of self-assembled HAs/Fe(3+) layers. Moreover, a 200 nm thick HAs/Fe(3+) film (in its hydrated state) had a shear modulus of about 80 MPa, implying stability upon implantation. These films were determined to be biocompatible since in vivo studies indicated only mild tissue reaction along with some neovascularization.

No abstract