Biomedical Engineering Reference
In-Depth Information
diseased tissues by utilizing certain cues that are specific to the targeted
tissue/cell to trigger the release of the encapsulated drug from the particulate
carriers. This need catalyzed the development of “smart” particles, which are
fabricated using stimuli-sensitive polymers that can sense and respond to small
changes in environment conditions such as pH, temperature, light, and ionic
strength. [6] We are particularly interested in pH-sensitive polymers, which are
characterized by their unique ability to sense small changes in environment pH
that trigger a corresponding change in the polymer's physical properties such
as size, shape, hydrophobicity, and/or degradation rate. [2, 7, 8] Earlier studies
showed that cross-linkage of pH-sensitive polymers yields “smart” hydrogels
with tunable swelling behavior, which have been used as carriers for controlled
drug delivery (Figure 1). In this chapter, we discuss the potential of “smart”
particles developed using pH-sensitive polymers as carriers for delivery of a
wide range of therapeutic molecules. [9-16]
1.1.
pH-sensitive polymers with acidic functional groups
One class of pH-sensitive polymers is known as polyelectrolytes or polyanions,
which is characterized by a large number of ionizable acidic groups such as
carboxylic or sulfonic acid groups (Figure 2). Examples of common polyanions
(A)
(B)
(C)
(D)
(E)
(F)
Fig. 2. The chemical structures of: (A) acrylic acid, (B) methyl acrylic acid, (C) ethyl acrylic acid,
(D) propyl acrylic acid, (E) butyl acrylic acid, and (F) sulfonic acid monomers used to synthesize
“smart” pH-sensitive polymers.
used in drug delivery include poly(acrylic acid) and poly(sulfonic acid)
polymers. The pendant acidic groups of these polymers are typically ionized in
neutral and alkaline solutions and their electrostatic repulsion affects the physical
properties of the polymer. The pH at which the pendant acidic groups become
ionized depends on the pKa (the log value of the acid dissociation constant) of
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