ABSTRACT
Efficient chemotherapy requires that the anticancer drug concentration in the
blood be maintained between the minimum effective therapeutic level and the
maximum tolerable level for long enough period. For most anticancer drug
formulations, however, the drug concentration peaks much higher than the
maximum tolerable level immediately after administration, which causes serious
side effects and then decreases soon below the minimum effective therapeutic
level, which makes the therapy inefficient. Frequent administration is thus
needed to meet the therapeutic needs, which, due to the extreme toxicity of
the anticancer drugs, may not be tolerable for the patients. Nanoparticles (NPs)
of biodegradable polymers may provide an alternative solution to maintain
the drug concentration within the therapeutic window for a prolonged time
(sustainable chemotherapy) [1-3]. The side effects and the administration
frequency can thus be reduced. To fulfill this aim, however, one prerequisite
is that the NPs can avoid elimination by the reticuloendothelial system (RES)
to stay in the circulation system for long enough period [4-6]. To suppress
the phagocytosis, colloidal particles are generally coated by the polyethylene
glycol (PEG), since the flexible and hydrophilic PEG layer is able to minimize the
recognition and uptake by the RES [7-12].
