Biomaterial-Based Particulate Drug Carriers - Harnessing Biomaterials in Nanomedicine: Preparation, Toxicity, and Applications - page 12

treatment of a particular pathology. We contend that the driving
force should be the therapeutic needs and the strongly related
choice of administration route. This concept will be discussed below,
supported by specific examples.
For particulate carriers, the term “passive targeting” 3 has been
coined for cases where the therapeutic targets are cells of the
reticuloensothelial system (RES), which tend to internalize particles
[45-50]. If, on the other hand, the therapeutic targets are not within
the RES, “active targeting” is called for, and requires two types of
eff orts that may be at odds with each other. One type of eff ort is to
endow the particles with the ability to avoid uptake by the RES and
to circulate long. The other type of eff ort is to endow the carrier with
the ability to bind with high affinity to sites unique to the target (as
has been discussed in Section 1.1.4). When and how this relates to
pathology-driven selection of carrier is discussed below.

1.3.2 Systemic Administration, Passive and Active

Targeting

Passive and active carrier-mediated drug targeting are particularly
relevant for therapies that require systemic administration. If the
pathology to be treated resides within RES cells, then carriers that fit
passive targeting are the systems of choice. Veteran and extensive in
vitro and in vivo studies made it clear that RES cells internalize micro-
sized particles such as liposomes and microspheres significantly
better than nano-sized particles [45-50]. Within microparticles
for RES therapy, further selection and caution are required with
respect to the loci of drug action. Taking, for example, macrophages
as a therapeutic target for a drug that operates inside the cell — for
such cases, conventional (regular) multilamellar liposomes (MLV)
internalized by these cells are an obvious carrier choice. If, however,
the macrophage-intended drug operates on its cell membrane, the
conventional MLV are the wrong choice, as they will deliver the drug
to the wrong place. For such therapies, even though the therapeutic
target is an RES cell, active targeting will be needed — using particles
that preferentially bind to the macrophage but are not internalized.
As already stated in this chapter, selecting a targeter that can provide
the carrier with active targeting is a case-by-case issue; specific
examples are given below.