STIMULI-SENSITIVE PARTICLES FOR DRUG DELIVERY - Biologically-Responsive Hybrid Biomaterials - page 172

Fig. 10. A schematic drawing showing a “smart” particle fabricated using an anionic polymer (e.g.
poly(acrylic acid)) to encapsulate a peptide/protein drug. In the acidic environment of the stomach,
the carboxylic acid groups of the polymer are unionized and the particle retains its therapeutic
cargo. However, once this particle reaches the small intestine, the carboxylic acid group becomes
ionized and the particle swells due to the electrostatic repulsion between the ionized groups, thus
releasing the encapsulated drug into the intestine to be absorbed.
drug into the duodenum compared to those with a higher content of the
hydrophobic NIPAM monomer. [92]
To achieve efficient delivery of peptide/protein drug molecules to the ileum,
the encapsulating carrier should have a higher pKa value than the ileum pH (6.0).
Dowding and co-workers developed a gel mixture of NIPAM with N-N'-
methylenebisacrylamide (BA) using 2% w/w of MAA as a cross-linking agent.
The MAA units in this gel have a pKa of 6.7, which caused the hydrogel to swell
in the ileum in response to environment pH. [85] Eaimtrakam et al. was the first
to develop a four-layer carrier system that incorporated water-insoluble
ethylcellulose and an enteric coating composed of each of the Eudragit
copolymers, which are anionic acrylic-based polymers. Results showed that the
S-100 polymer coat with the pKa of 6.8 (1:2 carboxyl:ester groups) swelled and
adhered to the ileum wall for up to three hours after administration, which
shielded the encapsulated drug molecules from the hydrolytic enzymes
commonly present in the duodenum. [93] Venkatesh et al. compared the release
profile of 15 mg of pindolol coated with either ethylcellulose (0.5% w/v) or a