DESIGN AND SYNTHESIS OF ENDOSOMOLYTIC CONJUGATED POLYASPARTAMIDE FOR CYTOSOLIC DRUG DELIVERY - Biologically-Responsive Hybrid Biomaterials - page 188

behavior between pH 6.4 and 6.8 with DS of API by protonation of imidazole
groups, which was in the range of endosomal pH.
Thermoresponsive poly( ŋ - N -substituted ȳ -glutamine)s and poly( N -
substituted ŋ / Ȳ -asparagine)s were developed by Kobayashi an coworkers by
grafting 5-aminopentanol and 6-aminohexanol onto poly( ȳ -glutamic acid) and
PSI. [28, 29] As shown in Figure 10, the LCST increased from 23 °C to 44 °C
with the content of 5-aminopentanol increased from 50% to 80%. This sharp
LCST of poly(amino acid) derivatives similar to poly( N -isopropylacrylamide)
(PNIPAM) is caused by hydrogen bonding between the amide bond in polymer
backbone and water molecules.
Fig. 10. Effect of temperature on light transmittance of 1 wt% aqueous solution of
thermoresponsive poly(amino acid)s. The content of 5-5-aminopentanol is 50% (A), 60% (B), 70%
(C), and 80% (D). (Tachibana, Y., et al., “Biodegradable Thermoresponsive Poly(amino acid)s”,
Chem. Comm. , 2003, 106-107. With permission).
6. pH-Sensitive Properties
A variety of pH-sensitive polymers have found wide applications in biomedical
and pharmaceutical fields, as they enhance drug release responses to pH changes
in the physiological environment such as the intestine, stomach, endosome, and
tumor. A pH-sensitive polyaspartamide derivative can conveniently be prepared
by grafting various cationic or anionic function groups to a polymer backbone.
Among the many ionic functional groups, the imidazole group with a pK a value
of 6.0 ~ 6.5 has an electron lone pair on the unsaturated nitrogen, and is easily
protonated in a slightly acidic environment. Thus, imidazole-containing pH-
sensitive polymers have attracted a great deal of attention in intracellular drug