Fabrication and characterization of surface-bound liposomes for biomedical applications

Abstract

Injectable liposomes are well known in the pharmaceutical industry for drug delivery. In particular, PEG-coated liposomes have found application for reason of their increased circulation time, which is believed to be associated with their low tendency to be opsonized. However, much of the drug never reaches the intended target site. In this study, methods for binding liposomes onto surfaces ofbiomaterials and biomedical devices were developed and applied for controlled local delivery of drugs adjacent to implanted biomedical devices. In this way the aim was to reduce drug amounts and wastage, and control the local host response to the implant, a response which with most current biomaterials typically is dominated by fibrous tissue encapsulation. Liposomes with encapsulated drugs and model substances were produced and characterized in terms of size and release performance, and bound onto polymeric surfaces. PEGylated phospholipid liposomes were produced by extrusion through polycarbonate membranes of various pore sizes. The diameters (mean and distribution) of the liposomes were characterized by photon correlation spectroscopy. For binding liposomes, polymer surfaces were coated with NeutrAvidin™, which was used for affinity capture ofbiotinylated PEGylated liposomes. NeutrAvidin™ was either covalently bound onto polymer surfaces via plasma (glow discharge) polymer coating and layers of carboxylated polymers (polyacrylic acid or carboxymethyl-dextrans) or affinity "docked" onto a PEG-Biotin gel interlayer. Detailed surface analyses (mainly X-ray Photoelectron Spectroscopy (XPS) and Atomic Force Microscopy (AFM)) were used to characterize and verify each step in the fabrication of the liposome coated surfaces. To test the in vitro efficacy ofliposome coated biomaterials, a compound known to modulate angiogenesis was encapsulated in liposomes and these liposomes attached onto solid surfaces. Results obtained with two in vitro angiogenesis model assays show that effective inhibition of angiogenesis was achieved with suitably constructed surfacebound liposome implants. The results presented in this thesis show that surface attachment of liposomes to modified polymers is feasible. Moreover, surface-bound liposomes can be successfully used as a drug delivery system to inhibit angiogenesis.