Biomedical Engineering Reference
In-Depth Information
methods of synthesizing dendrimers are classifi ed into (i) convergent and (ii)
divergent approaches. The synthesis process involves repetitive coupling and acti-
vation steps, which makes it diffi cult to obtain dendrimers in high yield, at reason-
able cost. These barriers have defi nitely limited the application of dendrimers
primarily in biomedical fi eld [7] .
Dendrimers differentiate themselves largely from hyperbranched polymers in
terms of their controlled size and shapes as well as narrow polydispersity [9].
Conversely, in linear polymers, the infl uence of end groups on physical properties
such as solubility and thermal behavior is negligible at infi nite molecular weight.
However, in dendritic polymers, the situation is quite different. The fraction of
end groups approaches a fi nal and constant high value at infi nite molecular
weight, and therefore, the nature of the end groups is expected to strongly infl u-
ence both the solution and the thermal properties of a dendrimer [10]. An explo-
sion of interest has been fueled due to chemicophysical properties in dendritic
macromolecules to be versatile nanomaterials, such as peripheral reactive end
groups, viscosity, or thermal behavior, and differ signifi cantly from those of linear
polymers [11]. Till date, a variety of hyperbranched dendrimers and their polymeric
architectures (e.g., polyglycerol (PG) dendrimers) have been implicated for diverse
applications in the form of drug encapsulation, catalysis, and polymerization ini-
tiators [12 - 14] .
This chapter highlights an overview on biodegradable dendrimers. More specifi -
cally, design of biodegradable dendritic architectures has been discussed keeping
focus on challenges in designing such dendrimers; their relation of biodegradabil-
ity and biocompatibility, and its biological implications.
Tomalia and Newkome
et al.
introduced well - defi ned and highly branched den-
drimers [5, 15], and almost a decade later, the fi rst form of biodegradable den-
drimer was simultaneously published by various groups [16 - 18] . Groot
et al.
reported a biodegradable form of dendrimers that have been built to completely
and rapidly dissociate into separate building blocks upon a single triggering event
in the dendritic core [17]. These dendrimers collapse into their separate mono-
meric building blocks after single (chemical or biological) activation step that
triggers a cascade of self-elimination reactions, thereby releasing the entire end
groups from the periphery of the “exploding” cascade-release dendrimer. Thus,
such multiple-releasing dendritic systems have been termed as “cascade-releasing
dendrimers.” The degrading dendritic system possesses two major advantages
over the conventional dendrimers: (i) multiple covalently bound drug molecules
can be site- specifi cally released from the targeting moiety by a single cleaving step,
and (ii) they are selectively as well as completely degraded and therefore can be
easily drained from the body [17].
Fascinatingly, Suzlai
et al.
demonstrated that the linear dendrimer could undergo
self- fragmentation
through a cascade of cleavage reactions initiated by a single trig-
gering event [18]. The degradation of dendrimer cleavage eventually leads to two
subsequent fragmentations per subunit, or geometric dendrimer disassembly.
Overall, the concept of “dendritic amplifi cation” was disclosed, in which an initial
stimulus triggers the effi cient disassembly of a dendrimer resulting in the ampli-
