Drug Targeting Organ-Specific Strategies

1.2.7 Polymeric Micelles
Polymeric micelles are characterized by a core-shell structure [32]. They have a di-block
structure with a hydrophilic shell and a hydrophobic core. The hydrophobic core generally
consists of a biodegradable polymer that serves as a reservoir for an insoluble drug. Non- or
poorly biodegradable polymers can be used, as long as they are not toxic to cells and can be
renally secreted. If a water-soluble polymeric core is used, it is rendered hydrophobic by
chemical conjugation with a hydrophobic drug. The viscosity of the micellar core may influence
the physical stability of the micelles as well as drug release. The biodistribution of the
micelle is mainly dictated by the nature of the shell which is also responsible for micelle stabilization
and interactions with plasma proteins and cell membranes. The micelles can contain
functional groups at their surface for conjugation with a targeting moiety [32].
Polymeric micelles are mostly small (10–100 nm) in size and drugs can be incorporated by
chemical conjugation or physical entrapment. For efficient delivery activity, they should
maintain their integrity for a sufficient amount of time after injection into the body. Most of
the experience with polymeric micelles has been obtained in the field of passive targeting of
anticancer drugs to tumours [33]. Attachment of antibodies or sugars, or introduction of a
polymer sensitive to variation in temperature or pH has also been studied [32].
1.2.8 Cellular Carriers
1.2 Carriers used in Drug Targeting 7
Cellular carriers may have the advantage of their natural biocompatibility. However, they
will encounter endothelial barriers and can rather easily invoke an immunological response.
Most of the approaches on cellular carriers have been applied to the field of cancer therapy.
Antigen specific cytotoxic T lymphocytes have been studied as vehicles to deliver immunotoxins
to cancer cells in vivo. To achieve this, a CD8 positive T-cell line that specifically recognized
a murine leukaemia cell line was transfected with a retroviral vector encoding a
truncated diphtheria-toxin molecule/IL-4 fusion protein. Intravenous injection of these
transfected cells led to significant tumour growth inhibition without concomitant renal and
hepatic toxicity common to this class of immunotoxins [34]. Whereas in this particular study
the intrinsic capacity of T cells to home to tumour tissue was exploited,Wiedle et al. attached
a homing device to a lymphoid cell line to improve homing ability [35]. By transfection of the
lymphoid cells with a chimeric adhesion molecule consisting of the CD31 transmembrane
domain and the disintegrin kristin, the lymphocytes specifically homed to αvβ3 expressing
pro-angiogenic tumour endothelium.
The identification of endothelial progenitor cells in peripheral blood [36], has led to the
hypothesis that these cells may in the future be exploited as drug carriers. It has been shown
that in diseases in which angiogenesis and/or vasculogenesis plays an important role, these
progenitors represent a pool of cells that seed at the site of neovascularization [37]. In theory,
one can isolate the progenitors from the peripheral blood and transfect them ex vivo with
genes encoding e.g. anti-angiogenic proteins. Subsequent intravenous or local re-injection of
the cells into the patient may lead to seeding of the transfected cells at the diseased site and
hence, local delivery of the therapeutic protein of interest [38].