Biomedical Engineering Reference
In-Depth Information
injections of antibody 38C2 and systemic treatments with an etoposide pro-
drug [54] .
Tansey
et al.
described synthesis and characterization of branched poly(l -
glutamic acid) (PG) containing multiple PG chains centered on a PAMAM den-
drimer or PEI cores [55]. The branched PG polymers were obtained by
ring-opening polymerization of benzyl ester of l - glutamic acid
N
- carboxyanhydride
using PAMAM or PEI as the initiator. The polymers were degradable in the
presence of the lysosomal enzyme cathepsin B, albeit more slowly than linear
PG. Unlike conventional linear PG, each branched PG possessed multiple termi-
nal amino groups. This made it possible to attach multiple targeting moieties
selectively to the termini of branched PG. Conjugation of monofunctional or
heterodifunctional PEG to the chain ends of branched PG demonstrated in the
presence of side-chain carboxyl groups. Furthermore, folic acid, a model-targeting
moiety, and the near-infrared dye indocyanine green, a model diagnostic agent,
were successfully conjugated to the terminal amino groups and the side- chain
carboxyl groups of branched PG, respectively. The resulting conjugate had
reduced nonspecifi c interaction and bound selectively to tumor cells expressing
folate receptors. Thus, branched PG may be useful as a polymeric carrier for
targeted drug delivery.
Degradable dendrimer architectures can be conjugated with linearly branched
polymers (PEG) to improve biological application due to the enhanced pharma-
cokinetic ability [27]. For example, van der Poll reported effi cient synthesis of a
robust and biodegradable PEGylated dendrimer based on a polyester-polyamide
hybrid core (synthesis section, Schemes 10.8-10.10 [27]). The architecture has
been designed to avoid destructive side reactions during dendrimer preparation
while maintaining biodegradability. Dendrimer functionalized with DOX was also
prepared from commercial starting materials in nine, high-yielding linear steps.
Both the dendrimer and Doxil were evaluated in parallel using equimolar dosage
in the treatment of C26 murine colon carcinoma, leading to statistically equivalent
results with the most mice tumor-free at the end of the 60-day experiment. The
attractive features of this dendritic drug carrier are its simple synthesis, biodegrad-
ability, and capability to deliver high payload of drugs.
Similarly, many glycol-dendrimers have been reported for applications in
biology. For example, glycopeptide dendrimers containing
ω
- amino acids (Gly,
β
-aminohexanoic acid) are of interest for immunological studies
[56] . Interestingly, biodegradable forms of dendrimers have been used as pH-
sensing biodegradable near-infrared nanoprobe capable of providing complemen-
tary information through both fl uorescence lifetime measurements and signal
amplifi cation in acidic environments
in vivo
[57]. Such tools may fi nd extensive
role in drug delivery systems, and such noninvasive approach may shed light on
the kinetics of such drug delivery strategies
in vivo
in a cost-effective and more
accurate manner.
It has been realized that in many cases the prepared dendrimeric structures are
more a result of an intellectual capability to prepare some unusual compounds
with new cores, branches, etc., than an exact approach based on the knowledge of
- Ala,
γ
- abu, and
ε
