Surface-modified nanocrystalline ceramics for drug delivery applications.

Drug delivery systems comprised of various types of carriers have long been the object of pharmacological investigation. The search has been stimulated by the belief that carriers will lead to reduced drug toxicity, dosage requirements, enhanced cellular targeting and improved shelf-life. Among the carriers investigated are complex polymeric carbohydrates, synthetic proteins and liposomal structures. For the past four years, we have been experimenting with a radically new class of carriers comprised of surface-modified nanocrystalline ceramics. While the ceramics provide the structural stability of a largely immutable solid, the surface modification creates a glassy molecular stabilization film to which pharmacological agents may be bound non-covalently from an aqueous phase with minimal structural denaturation. As a consequence of maintained structural integrity and owing to concentration effects afforded by the surfaces of the nanocrystalline materials, drug activity following surface immobilization is preserved. We have used successfully surface-modified nanocrystalline ceramics to deliver viral antigens for the purpose of evoking an immune response, oxygenated haemoglobin for cell respiration and insulin for carbohydrate metabolism. The theoretical principles, technical details and experimental results are reviewed. Surface-modified nanocrystalline materials offer an exciting new approach to the well-recognized challenges of drug delivery.

High-purity resident tissue macrophage isolates from human synovium and periprosthetic tissues using immunomagnetic techniques.

Destruction of periarticular and periprosthetic bone by activated macrophages, a process often termed "macrophage mediated osteolysis," is recognized as a leading mechanism of aseptic arthroplasty failure. To develop effective interventional approaches and increase the longevity of implanted joint prostheses, the pathobiology of activated human-synovium-derived macrophages needs to be better characterized. The first step toward achieving this research objective is the acquisition of pure populations of macrophages from human synovial tissue. A simple, fast, and highly efficient method for isolating a relatively pure population of macrophages from periprosthetic tissue received from either primary or secondary arthroplasty is presented. This technique uses murine monoclonal antibodies (IgG) that recognize a phagocyte-specific marker, CD68, for primary binding, and sheep anti-murine IgG antibodies bound to polystyrene-coated magnetic microspheres for secondary binding. While the primary antibody specifically labels CD68-positive phagocytes in the digestion of synovial and periprosthetic tissue, the secondary antibody bound to polystyrene-coated iron oxide beads facilitates the removal of CD68-positive cells from CD68-negative cells by anchoring the former with a magnet. This protocol requires centrifugation only in the washing steps, which reduces the frequency of cell death and altered cell morphology. The patient population includes three primary and eight revision arthroplasties. The tissue macrophage isolation protocol yielded on average 4 x 10(5) cells/g tissue, of which 91% were viable nonspecific esterase positive macrophages. The experimental results suggest that immunomagnetic beads coupled to anti-CD68 enable the isolation of a purified population of resident tissue macrophages suitable for further biologic characterization.