Fabrication and characterization of surface-bound liposomes for biomedical applications

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