The artificial cell design: liposomes - Artificial Cells, Cell Engineering and Therapy - page 77

across the intestinal mucosa into the circulation or the lymphatics. Passage
across enterocytes by diffusion is restricted to small, lipophilic molecules, and
transcytosis, which is rare, to particles less than 200 nm in diameter. Passage by
the paracellular pathway is impossible if the tight junctions are intact. Never-
theless, a number of studies have reported the appearance of particles in the
circulation after oral dosing (reviewed in Shakweh et al., 2004).
Other routes of administration
When colloidal drug carriers are administered by other routes, e.g. subcutaneous
or intramuscular injection or topical application, they are generally retained at
the site of administration longer than free drug. When a liposome-associated
drug is applied to the skin, the amount penetrating into the superficial layers may
be increased compared with free drug, while its passage to the systemic
circulation may be reduced (Mezei, 1988). After subcutaneous or intraperitoneal
administration, small liposomes may be taken up by regional lymph nodes
(Hawley et al., 1995). Liposomes instilled into the eye are also retained at the
site of administration, leading to important therapeutic potential in this area
(Kaur et al., 2004).
3.3.2 Therapeutic potential of conventional liposomes
The therapeutic potential of liposome-based systems is influenced by their
distribution, as described above. This section describes the possible spheres of
application of `conventional' liposomes by different routes of administration.
Structural modifications designed to modify their distribution will be discussed
in the following section.
Administration by the intravenous route
The potential applications by the intravenous route can be summarized as con-
centrating drugs in accessible sites, re-routing drugs away from sites of toxicity
and increasing the circulation time of labile or rapidly eliminated drugs (e.g.
peptides and proteins).
Delivery to macrophages
Since colloidal drug carriers are naturally concentrated within macrophages, it is
logical to use them to deliver drugs to these cells. A good example is the
delivery of muramyldipeptide (MDP) and chemically related compounds to
stimulate the antimicrobial and antitumoral activity of macrophages. MDP is a
low molecular weight, soluble, synthetic compound based on the structure of
peptidoglycan from mycobacteria, and, although it acts on intracellular