Biomedical Engineering Reference
In-Depth Information
biological activities, since it is not clear which part of the polymers with heteroge-
neous molecular weights is predominantly responsible for producing the unde-
sired effect [32]. In order to minimize the heterogeneity, novel synthetic methods
have to be employed for the preparation of polymers, and dendrimers for overcom-
ing this heterogeneity, with the potential advantages of unimolecular homogeneity
and defi ned chemical structures [33].
There have been numerous limitations to use poly(amidoamine) (PAMAM)
dendrimers for biomedical applications due to their nonbiodegrading traits. Nev-
ertheless, these polymers have shown to be biocompatible and can be easily
prepared with various surface functionalities, such as
OH
groups, and are commercially available up to generation 10 (G10) [7]. Even though
most applications of PAMAM are studied
in vitro
, a wide range of biomedical
applications has been proposed in the fi elds of gene delivery [34], anticancer
chemotherapy [35], diagnostics [36], and drug delivery [37, 38]. The cytotoxicity
of PAMAM dendrimers is diffi cult to generalize and depends on their surface
functionality, dose, and the generation of the dendrimers; however, the nonbio-
degradable nature of PAMAM is one of the reasons for its toxicity [39]. Toward
this end, more insights were recently described by Khandare
et al.
with respect
to the structure-biocompatibility relationship of dPG derivatives possessing
neutral, cationic, and anionic charges [40].
In vitro
toxicity for various forms of
dPGs was reported and compared with PAMAM dendrimers, polyethyleneimine
(PEI), dextran, and linear polyethylene glycol (PEG) using human hematopoietic
cell line U-937. It has been reported that dPGs possess greater cell compatibility
similar to linear PEG polymers and dextran, and is therefore suitable for develop-
ing sysmetic formulation in therapeutics [40].
Polymeric and dendritic carrier systems are expected to possess suitable physi-
cochemical properties for improved bioavailability, cellular dynamics, and target-
ability [23]. This is particularly true if the polymeric architectures have high surface
charge, molecular weight, and a tendency to interact with biomacromolecules in
blood due to their surface properties [40]. Most of the hyperbranched polymeric
architectures consisting of bioactive therapeutic agents are administered by a
systemic route. Therefore, their fate in blood and interactions with the plasma
proteins and immune response are very critical to establish the overall biocompat-
ibility. Studies in this direction have established the molecular and physiological
interactions of the dendritic polymers with plasma components [41].
Conclusively, biodegradable dendrimers and its other architectures ideally
should possess the following traits: (i) nontoxic, (ii) nonimmunogenic, and (iii)
preferably be biocompatible and biodegradable. In this last instance, one of the
potential virtues of dendrimers other than biodegradability comes under the
heading of “ multivalency ” - the enhanced effect that stems from lots of identical
molecules being present at the same time and place. Such simultaneous combina-
tion of multivalency and biodegradability with precision architectures can make
dendrimers a greater versatile platform with many interesting biomedical applica-
tions, not least for the drug delivery [42].
−
NH
2
,
−
COOH, and
−
