Biomedical Engineering Reference
In-Depth Information
initiating a cascade of “elimination” reactions leading to release of drug molecules
(Figure 10.1b). The dendritic forms with many identical units mean that ampli-
fi cation can be achieved as a kind of explosion. However, there could be a possible
drawback since if such a system is activated at the wrong time or place, the result
could be devastating [17]. The details of design and synthesis of such degradable
scaffolds have been discussed in the text below.
Several biodegradable polymers, dendrimers, and their prodrugs have been
widely used as drug carriers [20, 21]. Recently, dendrimer carriers based on poly-
ethers, polyesters, polyamides, melanamines or triazines, and several polyamides
have been explored extensively [13, 22, 23]. Other forms, for example, dendritic
polyglycerols (dPGs) are structurally defi ned, consisting of an aliphatic polyether
backbone, and possessing multiple functional end groups [14, 24]. Since dPGs are
synthesized in a controlled manner to obtain defi nite molecular weight and narrow
molecular polydispersity, they have been evaluated for a variety of biomedical
applications [25]. Hyperbranched PG analogs have similar properties as perfect
dendritic structures with the added advantage of defi ned mono- and multifunc-
tionalization [13, 14]. Additionally, Sisson
et al.
demonstrated PGs functionalized
by emulsifi cation method to create larger micogel structures emphasized for drug
delivery [26]. Among plethora of dendritic carriers, polyester dendrimers represent
an attractive class of nanomaterials due to their biodegradability trait; however,
the synthesis of these nanocarriers is challenging because of the hydrolytic sus-
ceptibility of the ester bond [27, 28]. In contrast, polyamide- and polyamine-based
dendrimers could withstand much wider selection of synthetic manipulations, but
they do not degrade as easily in the body and thus they may be more prone to
long - term accumulation
in vivo
.
Grinstaff recently described biodendrimers comprising biocompatible mono-
mers [21] using natural metabolites, chemical intermediates, and monomers of
medical-grade linear polymers. Interestingly, these dendritic macromolecules
(e.g., poly(glycerol-succinic acid) dendrimer) (PGLSA) are foreseen to degrade
in vivo
(Scheme 10.1). Furthermore, these dendrimers have been tuned for degra-
dation rate and the degradation mechanism for future
in vivo
applications.
10.2
Challenges for Designing Biodegradable Dendrimers
Biological applications of dendrimers have paved far ahead, comparatively over to
its newer forms of core designs-exhibiting biodegradability. As a consequence to
obtain a universal biodegradable, yet highly aqueous soluble and unimolecular
dendrtic carrier capable of achieving high drug pay loading remains to be an
unmet challenge. The greater aspect is to limit the early hydrolysis of the polymeric
chains at the core compared to the periphery. Therefore, the prime objective
remains to design biodegradable dendrimers having precise branching, molecular
weight, monodispersity, and stable multiple functional appendages for covalent
attachment of the bioactives.
