Recent Progress in Polymer Therapeutics as Nanomedicines - Harnessing Biomaterials in Nanomedicine: Preparation, Toxicity, and Applications - page 104

Their stability, monodispersity, and, especially, multivalency make
the dendrimers attractive candidates for drug delivery. Although there
is a massive research in that direction, this field is still in a preliminary
stage and only few in vivo studies have been reported. Well-known
commercialized dendrimers are polypropyleneimine (PPI) and
polyamido amine (PAMAM), both carrying cationic surface groups.
Cationic dendrimers are attractive mainly as nucleic acids carriers,
as will be discussed later. However, cationic dendrimers interact non-
specifically with negatively charged biological membranes, which
results in toxicity. Conversely, anionic or neutral dendrimers are
non-toxic [142, 143]. Most current eff orts are focused at lowering
the toxicity and utilizing dendrimers as therapeutic nano-carriers
either by developing biocompatible and biodegradable dendrimers,
or by surface modifications of dendrimers. Various biocompatible
dendrimers have been developed such as citric acid dendrimers
[144], phosphate dendrimers [145], and lysine dendrimers [146].
Biodegradable dendrimers such as polyester dendrimers [147],
polyether dendrimers [148] and triazine dendrimers [149] have
also been examined. Another promising approach is modifying the
surface of dendrimers with various functional groups, thus masking
the cationic charge of the dendrimers and gaining functionality.
Examples for surface functionality are targeting and enhanced
cellular internalization moieties, drug or DNA/RNA complexation or
conjugation, improved pharmacokinetic properties by PEGylation,
etc. Singh et al. [150] used 4G PAMAM dendrimers conjugated to folic
acid through PEG spacer and loaded them with anti-cancerous drug
5-fluorouracil (5-FU). Their results indicated that this dendrimer
conjugate is significantly safer and more eff ective in tumor targeting
compared with free drug and non-PEGylated formulation. Another
interesting utilization of dendrimers is for imaging, as was explored
by Zhang et al. [151]. 5G PAMAM dendrimers were radiolabeled
with 99m Tc that were similarly conjugated to PEG and folic acid, and
successfully used in micro-SPECT (single photon emission computed
tomography) imaging of KB tumor bearing nude mice, showing
specific accumulation in tumors.
4.5.3 TheInfl uence of Shape on Performance
Although the elegance of dendritic and micellar systems aesthetically
appeals to us, we should ask ourselves what the true advantages