parts [140]. The initial burst release values of DOX from chitosan and folateconjugated chitosan nanoparticles were 19.6% and 22.4%, respectively, in the
first 24 h followed by a constant sustained release of the drug. The release profiles
were quite similar to those obtained for chitosan nanoparticles reported elsewhere
[141–143], for which the kinetics often follow the first-order rate law [144]. The
cellular uptake rate of the folate-conjugated chitosan nanoparticles was relatively
faster than that of the chitosan nanoparticles. This could be due to the more
effective folate-mediated endocytosis. Both types of nanoparticles exhibited similar
toxicity profiles against MCF-7 cancer cells. Here also, the results indicated that the
lower cell viability corresponded to a higher DOX concentration and longer
incubation time. These core–shell nanoparticles are very promising as delivery
vectors for the treatment of tumors, especially breast cancer, for which folate
receptors are overexpressed.
To date, biodegradable thermoresponsive drug carriers are being purposely
engineered and constructed with nanometer dimensions [145]. These approaches
make it possible to develop smart materials like thermoresponsive drug delivery
vehicles. Recently, poly(N-vinyl caprolactam) (PNVCL) has superseded the most
commonly used pH and temperature-sensitive polymer i.e. poly(N-isopropylacrylamide) (PNIPAAm) because of its superior thermoresponsive nature, complexation ability, and biocompatibility [146]. The most important advantages of these
thermoresponsive polymeric nanomaterials include their high tunability, through the
switch on and off mechanism, and good biodegradability because of the conjugation
with a biocompatible chitosan moiety [146]. Surprisingly, at present there are no
studies concerning the use of these nanoformulations for cancer therapy. However,
Rejinold et al. [146] reported the development of a nanoformulation of 5-fluorouracil
(5-FU) with biodegradable thermoresponsive chitosan-g-PNVCL nanoparticles
(TRC NPs) produced by an ionic crosslinking method. 5-FU, a pyramidine analog
that interferes with thymidylate synthesis against solid tumors [147], has a broad
spectrum of activity but possesses a short biological half-life due to rapid metabolism, incomplete and non-uniform oral absorption due to rapid metabolism by
dihydropyramidine dehydrogenase, and non-selective action against healthy cells.
This problem can be overcome by developing appropriate nanocarrier systems
that can efficiently release 5-FU to the target sites. Rejinold et al.146 showed that
the 5-FU drug release was more prominent above its lower critical solution temperature (LCST) (38
C) compared to release below the LCST. The 5-FU-TRC NPs
were toxic to PC3, KB, and MCF7 cancer cells, which indicated the inhibition to
cancer cells. Therefore, it can be said that the novel TRC NPs could be used as
promising cancer drug delivery vehicles when subjected to a temperature increase
using external sources.
The ionic gelation method has received tremendous attention in recent years for
the preparation of nanocarriers for low molecular drugs [148]. As far as chitosanbased nanoparticles are concerned, sodium tripolyphosphate (TPP) is usually used
as ionic crosslinking agent. Chitosan-based nanoparticles can also be prepared using
self-assembly methods. In this case, polyanionic compounds are selected and
then allowed to react separately with chitosan and modified chitosan. Electrostatic
Engineering of Polysaccharides via Nanotechnology
107
first 24 h followed by a constant sustained release of the drug. The release profiles
were quite similar to those obtained for chitosan nanoparticles reported elsewhere
[141–143], for which the kinetics often follow the first-order rate law [144]. The
cellular uptake rate of the folate-conjugated chitosan nanoparticles was relatively
faster than that of the chitosan nanoparticles. This could be due to the more
effective folate-mediated endocytosis. Both types of nanoparticles exhibited similar
toxicity profiles against MCF-7 cancer cells. Here also, the results indicated that the
lower cell viability corresponded to a higher DOX concentration and longer
incubation time. These core–shell nanoparticles are very promising as delivery
vectors for the treatment of tumors, especially breast cancer, for which folate
receptors are overexpressed.
To date, biodegradable thermoresponsive drug carriers are being purposely
engineered and constructed with nanometer dimensions [145]. These approaches
make it possible to develop smart materials like thermoresponsive drug delivery
vehicles. Recently, poly(N-vinyl caprolactam) (PNVCL) has superseded the most
commonly used pH and temperature-sensitive polymer i.e. poly(N-isopropylacrylamide) (PNIPAAm) because of its superior thermoresponsive nature, complexation ability, and biocompatibility [146]. The most important advantages of these
thermoresponsive polymeric nanomaterials include their high tunability, through the
switch on and off mechanism, and good biodegradability because of the conjugation
with a biocompatible chitosan moiety [146]. Surprisingly, at present there are no
studies concerning the use of these nanoformulations for cancer therapy. However,
Rejinold et al. [146] reported the development of a nanoformulation of 5-fluorouracil
(5-FU) with biodegradable thermoresponsive chitosan-g-PNVCL nanoparticles
(TRC NPs) produced by an ionic crosslinking method. 5-FU, a pyramidine analog
that interferes with thymidylate synthesis against solid tumors [147], has a broad
spectrum of activity but possesses a short biological half-life due to rapid metabolism, incomplete and non-uniform oral absorption due to rapid metabolism by
dihydropyramidine dehydrogenase, and non-selective action against healthy cells.
This problem can be overcome by developing appropriate nanocarrier systems
that can efficiently release 5-FU to the target sites. Rejinold et al.146 showed that
the 5-FU drug release was more prominent above its lower critical solution temperature (LCST) (38
C) compared to release below the LCST. The 5-FU-TRC NPs
were toxic to PC3, KB, and MCF7 cancer cells, which indicated the inhibition to
cancer cells. Therefore, it can be said that the novel TRC NPs could be used as
promising cancer drug delivery vehicles when subjected to a temperature increase
using external sources.
The ionic gelation method has received tremendous attention in recent years for
the preparation of nanocarriers for low molecular drugs [148]. As far as chitosanbased nanoparticles are concerned, sodium tripolyphosphate (TPP) is usually used
as ionic crosslinking agent. Chitosan-based nanoparticles can also be prepared using
self-assembly methods. In this case, polyanionic compounds are selected and
then allowed to react separately with chitosan and modified chitosan. Electrostatic
Engineering of Polysaccharides via Nanotechnology
107