The use of photosensitive erythrocytes in drug delivery

The development of systems capable of delivering therapeutic agents in a site-specific manner continues to attract considerable attention, particularly for the treatment of focal disease such as many forms of cancer. Although many forms of delivery systems have emerged over the past 2 decades, the focus of my work has been directed towards the study of the erythrocyte as a potential drug delivery vehicle for possible clinical application in the treatment of solid tumours. The erythrocyte, as a drug delivery vehicle, has attracted a considerable degree of attention in the past, although many of the suggested applications depend on either passive delivery of therapeutic agents or in facilitating fortuitous targeting modalities based on sequestration by the reticuloendothelial system (RES). To date no erythrocyte-based system exists where application of an external stimulus can facilitate site-specific release and deposition at a pre-determined target site. The work in this thesis, therefore, describes my attempts to develop and assess such a system in order to facilitate delivery of therapeutic effects to solid tumours. In pursuing such an objective, the work in this thesis describes the development and assessment of an erythrocyte-based carrier system in vitro, exploiting fluorogenic tracers to demonstrate light- and ultrasound-stimulated release from the carrier and retention of the released payload at a target site. The work in this thesis goes beyond the existing state-of-the-art in describing the behaviour of the system in a phantom-based circulation system in order to demonstrate functionality in terms of stimulus-dependant release of payload from the system. Building on those studies, the work in this thesis extends into in vivo studies in mice using the stimulus- responsive erythrocyte-based system to demonstrate deposition of a therapeutic at a target site. In these studies, Iight- and ultrasound-stimulated site-specific deposition of indocyanine green was demonstrated and this was further exploited in order to demonstrate a therapeutic effect (reduction in tumour growth) at the deposition site. The data in this thesis suggest a significant potential role for a stimulus-responsive erythrocyte-based carrier system, particularly in the treatment of solid tumours.EThOS - Electronic Theses Online ServiceGBUnited Kingdo