Biomedical Engineering Reference
In-Depth Information
delivery field due to their amphoteric, low-toxic, and ionic properties associated
with such pH sensitivity.[30, 31] Recently, a series of novel pH-sensitive
polyaspartamide derivatives with various DS of C18, MPEG and API were
prepared by successive graft reactions of C18, MPEG, and API onto PSI and
their pH-sensitive properties were investigated. They showed stable nano-
aggregates in PBS 7.4 and their size changed according to pH. These behaviors
were controlled by the DS of C18 and API. The polymers with a low DS of 8%
formed nano-aggregates above pH 6.8, while they were completely dissociated at
pH below 6.8. This aggregation behavior of C18/MPEG/API-g-polyaspartamides
is reversible. As shown in Figure 11, polymers with a high DS of 15% formed
stable nano-aggregates between pH 5 and pH 8. Their size slightly increased with
decreasing pH as the hydrophobic interactions with the octadecyl chains were
stronger than the repulsive interactions with the protonated imidazole groups
under acidic pH in the polymer system with low DS of octadecylamine. This was
contrary to the polymer system with a high DS of octadecylamine. These
aggregation behaviors of pH-sensitive polyaspartamides should have a
correlation with endosome lysis and drug release properties of polymers,
controlled by the DS of the ionic and hydrophobic groups.
300
C40-MPEG2-API58
C40-MPEG3-API57
C40-MPEG4-API56
C20-MPEG2-API78
C20-MPEG3-API77
C20-MPEG4-API76
(b)
(a)
300
200
200
100
100
0
0
5
6
7
8
4
5
6
7
8
9
pH
pH
Fig. 11. Particle size changes of C18/MPEG/API-grafted polyaspartamides with (a) 15% and (b)
32% of DS of C18.
Histidine- and octadecylamine-conjugated poly(2-hydroxylethyl)aspartamides
(PHEA-g-C18-His) were synthesized by Kim and coworkers via an ester linkage
using
N
-Boc-L-histidine, followed by deprotection of Boc groups as an
endosomolytic carrier for delivery of doxorubicin [32] and the chemical structure
is shown in Figure 12. The doxorubicin release from these polymer aggregates
was accelerated by decreasing the pH through ionization of the histidine groups,
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