important tools for biomaterial scientists, chitosan possesses unique properties that
have recently been used in a wide range of biomedical applications. Unlike other
polysaccharides, chitosan is polycationic in nature and, therefore, it is able to bind
negatively charged molecules [13]. On the other hand, chitosan offers the possibility
of modifying different chemical groups in its structure [131]. In order to realize its full
biochemical and biomechanical potential, biomaterial scientists are exploring ways to
engineer chitosan and chitosan-based nanostructures that can be used to tune the
response of biological systems (namely cells, tissues, etc.) to these materials [132].
9.1 Chitosan-Based Nanoparticles
The importance of chitosan-based nanoparticles is noteworthy in the context of
their biomedical applications. Various methods are available for nanoparticles
syntheses. In 2007, Zhang et al. [133] reported the synthesis of oleoyl-chitosan
(OCH) nanoparticles with an almost spherical shape and a mean diameter of
255.3 nm as drug carriers for doxorubicin (DOX) by oil-in-water emulsification
according to a published method [134]. In brief, OCH was dissolved in 0.1 M acetic
acid followed by subsequent addition of methylene chloride under stirring. Then,
the mixture was homogenized four times. The solution was held under vacuum for
2 h at 20
C to remove methylene chloride and then 1 mL of 0.25% sodium
tripolyphosphate solution was added as a crosslinker. DOX-OCH nanoparticles
were prepared in a similar way except that DOX was added to the OCH solution
before initiating homogenization. The authors evaluated the usefulness of OCH
nanoparticles as carriers for DOX by measuring their encapsulation efficiency, drug
release profile, and inhibitory rates for different human cancer cells (A549, Bel7402, HeLa, and SGC-7901) in vitro. The results indicated that the percentage
inhibitory rate of DOX solution and of a DOX-OCH nanoparticle suspension for all
cancer cells increased with an increase in DOX concentration and extension of
treatment, but that DOX-OCH nanoparticles showed better inhibition of cancer
cells than DOX itself [133].
In another study, Manaspon et al. [135] reported a drug delivery system using
folate-conjugated pluronic F127/chitosan core–shell nanoparticles for delivering
DOX to the target cancer cells in a different way. In this case, DOX was
encapsulated in pluronic F127 micelle cores in the presence of sodium dodecyl
sulfate (SDS) by a self-assembly method, which is a spontaneous process at or
above the critical concentration (CMC) of around 0.1% (w/v) [136–139]. This was
followed by forming a layer of either chitosan or folate-conjugated chitosan onto
the pluronic micelles via an electrostatic interaction. From the study of particle size
as well as zeta potential of both micelles, the DOX-loaded micelles were not
stable and could easily coagulate, which can be problematic for drug delivery
applications. To solve this problem, SDS was used to ameliorate the stability of
the micelles. Being an anionic surfactant, SDS can interact with pluronic micelles
by binding to the hydrophobic core followed by interaction with hydrophilic corona
106
J. Dutta
have recently been used in a wide range of biomedical applications. Unlike other
polysaccharides, chitosan is polycationic in nature and, therefore, it is able to bind
negatively charged molecules [13]. On the other hand, chitosan offers the possibility
of modifying different chemical groups in its structure [131]. In order to realize its full
biochemical and biomechanical potential, biomaterial scientists are exploring ways to
engineer chitosan and chitosan-based nanostructures that can be used to tune the
response of biological systems (namely cells, tissues, etc.) to these materials [132].
9.1 Chitosan-Based Nanoparticles
The importance of chitosan-based nanoparticles is noteworthy in the context of
their biomedical applications. Various methods are available for nanoparticles
syntheses. In 2007, Zhang et al. [133] reported the synthesis of oleoyl-chitosan
(OCH) nanoparticles with an almost spherical shape and a mean diameter of
255.3 nm as drug carriers for doxorubicin (DOX) by oil-in-water emulsification
according to a published method [134]. In brief, OCH was dissolved in 0.1 M acetic
acid followed by subsequent addition of methylene chloride under stirring. Then,
the mixture was homogenized four times. The solution was held under vacuum for
2 h at 20
C to remove methylene chloride and then 1 mL of 0.25% sodium
tripolyphosphate solution was added as a crosslinker. DOX-OCH nanoparticles
were prepared in a similar way except that DOX was added to the OCH solution
before initiating homogenization. The authors evaluated the usefulness of OCH
nanoparticles as carriers for DOX by measuring their encapsulation efficiency, drug
release profile, and inhibitory rates for different human cancer cells (A549, Bel7402, HeLa, and SGC-7901) in vitro. The results indicated that the percentage
inhibitory rate of DOX solution and of a DOX-OCH nanoparticle suspension for all
cancer cells increased with an increase in DOX concentration and extension of
treatment, but that DOX-OCH nanoparticles showed better inhibition of cancer
cells than DOX itself [133].
In another study, Manaspon et al. [135] reported a drug delivery system using
folate-conjugated pluronic F127/chitosan core–shell nanoparticles for delivering
DOX to the target cancer cells in a different way. In this case, DOX was
encapsulated in pluronic F127 micelle cores in the presence of sodium dodecyl
sulfate (SDS) by a self-assembly method, which is a spontaneous process at or
above the critical concentration (CMC) of around 0.1% (w/v) [136–139]. This was
followed by forming a layer of either chitosan or folate-conjugated chitosan onto
the pluronic micelles via an electrostatic interaction. From the study of particle size
as well as zeta potential of both micelles, the DOX-loaded micelles were not
stable and could easily coagulate, which can be problematic for drug delivery
applications. To solve this problem, SDS was used to ameliorate the stability of
the micelles. Being an anionic surfactant, SDS can interact with pluronic micelles
by binding to the hydrophobic core followed by interaction with hydrophilic corona
106
J. Dutta