Biomaterial-Based Particulate Drug Carriers - Harnessing Biomaterials in Nanomedicine: Preparation, Toxicity, and Applications - page 13

The preference RES cells show for micro- over nanoparticles
constitutes an essential, though not sufficient, clue to achieving active
targeting to non-RES cells upon systemic administration. It was
furthermore shown that when small particles are also coated with
agents such as polyethylene glycol (PEG) that delay opsonization,
RES avoidance and long circulation are much improved [2, 30, 31,
50-55]. These issues have been extensively reported and reviewed
and an interested reader is referred to these sources [2, 30, 31,
50-55]. A prominent example is the well-known clinically approved
Doxil, the PEGylated doxorubicin-loaded nano liposomes [51, 54,
56]. PEG, an agent that when coating a nanoparticle confers upon
it the ability for long circulation is not, however, a targeting agent.
In the area of cancer, eff orts are under way to add targeters such
as folate or antibodies to Pegylated nanoparticles [35, 57-59]. The
success of such approaches will obviously depend on the choice of
targeter and whether the opsonization-delay agent and the targeting
agent will not interfere with each other. Hyaluronan, when coating
particle surfaces, performs a dual role: Rich with hydroxyl residues
(much like PEG), hyaluronan coating confers long circulation; it is
also, as discussed in section 1.2.2, an eff ective tumor targeter. We
have shown this dual role for nano-sized liposomes encapsulating
doxorubicin or mitomycin C, which have hyaluronan as a targeter
attached to their surface and for nano-sized gagomers encapsulating
paclitaxel, in which hyaluronan is the surface [15, 30, 31].

1.3.3 Administration by Local Injection

For local injections of particulate carriers, restrictions on particle size
are less stringent than those discussed above for IV administration.
Carrier type and size can be selected to fit the specific treatment
modality and drug requirements. Local injection of a carrier
encapsulating a macromolecule that operates inside the cell, such
as in gene therapy or gene silencing, will require a diff erent type
of particle than for the smaller molecules such as antibacterial or
chemotherapeutic. As already said, for small drugs operating inside
a target cell, internalization may not be necessary. Carrier binding
to the cell membrane and retention there to allow sufficient drug
diff usion into the cell may well suffice. In such cases, micro-sized
particles are also a valid choice.