Drug Delivery Systems That Eradicate and/or Prevent Biofilm Formation - Antibiofilm Agents: From Diagnosis to Treatment and Prevention - page 405

3.2 Others Polymer-Based Drug Delivery Systems
The University of Washington Engineered Biomaterials group has developed a
novel drug delivery polymer matrix consisting of a poly(2-hydroxyethyl methac-
rylate) hydrogel coated with ordered methylene chains that form an ultrasound-
responsive coating. This system was able to retain the drug ciprofloxacin inside the
polymer in the absence of ultrasound, but showed significant drug release when
low-intensity ultrasound was applied (Norris et al. 2005 ).
4 Dendrimer-Based Drug Delivery Systems
Dendrimers are highly ordered and repeatedly branched globular macromolecules
produced by stepwise iterative approaches first described by Buhleier et al. ( 1978 ).
The structure of dendrimers consists of three distinctive architectural regions: a
core, layers of branched repeat units emerging from the core, and functional end
groups on the outer layer of repeat units (Grayson and Frechet 2001 ). Tomalia
et al. ( 1984 ) reported the synthesis and characterization of the first family of
polyamidoamine (PAMAM) dendrimers, which has developed into one of the
most accepted dendrimers since. Two synthetic approaches, divergent and conver-
gent, have been developed to synthesize dendrimer systems for delivering various
types of drugs. In the divergent approach, synthesis initiates from a core and
emanates outward through a repetition of coupling and activation steps. During
the first coupling reaction, the peripheral functional groups of the core react with
the complementary reactive groups to form new latent branch points at the coupling
sites and increase the number of peripheral functional groups. These latent func-
tional groups are then activated to couple with additional monomers. The activation
of the latent functional groups can be achieved by removal of protecting groups,
coupling with secondary molecules, or reactive functionalization (Fig. 4 ). Large
excess of reagents is required to drive the activation step to completion. The
resulting dendrimer products can then be separated from the excess reagents by
distillation, precipitation, or ultrafiltration.
In contrast, the convergent approach initiates the synthesis from the periphery
and progresses inward (Fig. 5 ). This approach starts with coupling end groups to
each branch of the monomer, followed by the activation of a single functional group
located at the focal point of the first wedge-shape dendritic fragment or dendron.
Higher generation dendron is synthesized by the coupling of the activated dendron
to an additional monomer. After repetition of the coupling and activation steps, a
globular dendrimer is formed by attaching a number of dendrons to a polyfunctional
core. Dendrimers thus synthesized can be effectively purified. However, synthesis
of large dendrimers above the sixth generation is difficult (Grayson and Frechet
2001 ).