Biomedical Engineering Reference
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the swelling ratio also increases with increasing temperature [45]. The stiffness and
hardness decrease with increasing the weight ratio of HA because of the soft mechanical
properties of HA [46].
HA interacts with proteins such as CD44 and fibrinogen, and has an important role
in many natural processes such as cell motility, cell adhesion, and wound healing.
Chondrocyte adhesivity and proliferation and the synthesis of aggrecan are significantly
higher in the chitosan/HA groups than in the pure chitosan group [47]. Cai and coworkers
[48] found that the chitosan/HA/collagen complex film possesses promising coagulation
capability, cell compatibility, and antibacteria property.
4.2.1.4 Chitosan/Heparin PECs
Chitosan/heparin PEC microparticles are prepared by one-shot addition or dropwise
titration using chitosan as the starting solution. In the pH range of 1.2-6.5, ionized chito-
san and heparin are able to form PECs, which result in a matrix structure with a spherical
shape. Outside this pH range, the nanoparticles become unstable and break apart (as
shown in Figure 4.3). This is because that at pH 7.0, chitosan is deprotonated, causing the
collapse of the nanoparticles. These observations suggest that nanoparticles with pH-
responsive characteristics (that are stable at pH 1.2-2.5 (simulating gastric acid)) are capable
of protecting drugs from destruction by gastric acids [49]. A low pH value of the chitosan
solution, a high chitosan M W and a high chitosan concentration and heparin concentration
all contributed to the large heparin/chitosan nanoparticles size [50]. And under conditions
Heparin (COOH; SO - ; NHSO - )
Heparin (COO - ; SO - ; NHSO - )
Heparin (COOH; COO - ; SO - ; NHSO - )
Heparin (COO - ; SO - ; NHSO - )
SO -
NHSO -
COOH
COOH
COO - COO -
SO -
NHSO -
COO -
SO -
NHSO -
COOH
COO -
COO -
SO -
NHSO -
NH +
NH +
NH +
NH +
NH +
NH +
NH +
NH +
NH +
NH +
Chitosan (NH + )
NH + NH +
NH 2
NH 2
NH 2
NH 2
Chitosan (NH + )
Chitosan (NH + )
Chitosan (NH 2 )
pH 1.2
pH 2.5
pH 4.5-6.5
pH 7.0
Moderate swelling
+
Aggregates
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
- - - -
-
+
-
-
-
-
+
+
+
- - -
+
+ +
+
+
- -
-
- - - -
-
-
+
--
+
-
+
+
+
+
- -
+
-
+
-
-
+
-
Figure 4.3
Schematic illustrations of the physical structures of chitosan/heparin nanoparticles in specific pH environ-
ments. (From Lin, Y. H. et al. 2009. Biomaterials 30: 3332-3342. With permission.)
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