Biomedical Engineering Reference
In-Depth Information
10
Biodegradable Dendrimers and Dendritic Polymers
Jayant Khandare and Sanjay Kumar
10.1
Introduction
The concept of using a polymer as a carrier for drug delivery system originated
from the hypothesis that macromolecules could be used to improve the solubility
and half-life of small molecule drugs [1, 2]. Later, it was observed that macro-
molecules functionalized with a drug in the form of prodrug impart added advan-
tage by increasing accumulation in tumor tissues due to the leaky vasculature,
now a concept recognized as
enhanced permeation and retention
effect [3, 4]. It has
been clearly demonstrated that the macromolecular carriers have immense poten-
tial to enhance pharmacokinetics, leading to enhance the effi cacy of small mol-
ecule drugs. Several carrier systems have been studied (viz., linear polymers,
micellar assemblies, liposomes, polymersomes, and dendrimers) and are observed
to have most of the properties required for ideal drug carrier [5]. Thus, it is not
surprising that the ideal drug carrier would facilitate long blood circulation time,
high accumulation in tumor tissue, high drug loading, lower toxicity, and simplic-
ity in preparation. Within the milieu of nanocarriers, dendrimers represent a
fascinating platform because of their nanosize, monodisperisty, and degree of
branching to facilitate the multiple attachments of both drugs and solubilizing
groups [6] .
Dendrimers are excellent candidates for providing a well-defi ned molecular
architecture, which is a result of a stepwise synthetic procedure consisting of
coupling and activation steps [7]. They consist of branched, wedge-like structures
called dendrons that are attached to a multivalent core, and emerge readily toward
the periphery. The architecture and synthetic routes result in highly defi ned den-
dritic structure with polydispersity index near 1.00, as opposed to the much higher
polydispersity of linear or hyperbranched structures [5]. The fl exibility to tailor both
the core and surface of these systems create them innovative
nanovehicle
, since
different groups can be provided so as to optimize the properties of drug carrier.
For instance, the functional periphery is one of the intriguing properties of den-
dritic architecture with extensive number of end groups that may be modifi ed to
afford dendrimers with tailored chemical and physical properties [8, 9]. The general
