hydrodynamic diameter (R d ) of the ORI-loaded nanogels was 99.6 nm, whereas the
R d of the blank nanogels was 81.2 nm, indicating that ORI molecules were successfully encapsulated and that these entrapped ORI increased the size of the ORI-loaded
nanogels. In vitro drug release studies indicated that ORI-loaded nanogels exhibited a
pH-triggered fast drug release under slightly acidic conditions. Moreover, the MTT
assay and cellular morphological analysis demonstrated that the ORI-loaded nanogels
could enhance the antitumor activity in an acidic environment. No significant cytotoxicity, however, was observed with the blank carriers themselves. Therefore, this
nanogel-based delivery system might be exploitable in tumoral acidic extracellular
pH targeting for hydrophobic anticancer drugs.
To deliver anticancer drugs at the targeted sites, the development of both biodegradable and biocompatible thermoresponsive carriers has received significant attention. Although, various polymers like gelatine [202], poly(vinyl alcohol) [203],
PNIPAAm, poly(N-isopropylmethacrylamide) [204, 205], hydroxypropyl cellulose
[206], etc. have been explored for use as temperature-triggered DDSs. Among them,
PNIPAAm seems to be a promising thermosensitive DDS because its transition
temperature (approximately 32–34
C) can be modulated near human body temperature [206–208]. However, one of the key challenges with the use of thermoresponsive PNIPAAm-based hydrogels is to modulate its LCST to around body
temperature and preferably up to 42–43
C, a temperature used for hyperthermia
treatment of cancer [209]. But, there is a issue with PNIPAAm in that it is not
biodegradable. Therefore, PNIPAAm gel particle surfaces need to be modified or
conjugated with some other biodegradable polymers in order to develop biodegradable DDSs [210]. In an attempt, Jaiswal et al. [211] demonstrated the synthesis and
characterization of temperature-optimized and magnetically modalized PNIPAAm–
chitosan-based nanohydrogels for possible application in hyperthermia for cancer
treatment. The particle size analysis data showed that the room temperature hydrodynamic diameters for all the hydrogel particles synthesized in different weight
proportions of NIPAAm and chitosan were in the size range of 100–300 nm.
The SEM and AFM micrographs of nanohydrogels and magnetic nanohydrogels
showed that there was a reasonable decrease in hydrogel size with an increase in the
chitosan to NIPAAm ratio, which was consistent with the hydrodynamic diameter
measurements obtained by DLS. This decrement might be attributed either to
the crosslinking of chitosan to PNIPAAm or due to its role as a surfactant, or both
[212, 213]. The observed change in LCST was attributed to hydrophilic modifications
of PNIPAAm by water-soluble N,N
0 -methylene-bis-acrylamide (MBAAm) [213]
and it was conceived that the associated shift in LCST was due to a decrease in
mobility of water molecules trapped in crosslinked chain pores, defined as bound
water molecules [214, 215]. Upon reduction in hydrogel size, pores of the mesh
diminish in size and, in turn, bound water volume decreases. But, they are held there
for a longer time with respect to temperature and that requires a higher amount of heat
energy to expel them. Consequently, the LCST shifted in an upward direction. So, it
118
J. Dutta
R d of the blank nanogels was 81.2 nm, indicating that ORI molecules were successfully encapsulated and that these entrapped ORI increased the size of the ORI-loaded
nanogels. In vitro drug release studies indicated that ORI-loaded nanogels exhibited a
pH-triggered fast drug release under slightly acidic conditions. Moreover, the MTT
assay and cellular morphological analysis demonstrated that the ORI-loaded nanogels
could enhance the antitumor activity in an acidic environment. No significant cytotoxicity, however, was observed with the blank carriers themselves. Therefore, this
nanogel-based delivery system might be exploitable in tumoral acidic extracellular
pH targeting for hydrophobic anticancer drugs.
To deliver anticancer drugs at the targeted sites, the development of both biodegradable and biocompatible thermoresponsive carriers has received significant attention. Although, various polymers like gelatine [202], poly(vinyl alcohol) [203],
PNIPAAm, poly(N-isopropylmethacrylamide) [204, 205], hydroxypropyl cellulose
[206], etc. have been explored for use as temperature-triggered DDSs. Among them,
PNIPAAm seems to be a promising thermosensitive DDS because its transition
temperature (approximately 32–34
C) can be modulated near human body temperature [206–208]. However, one of the key challenges with the use of thermoresponsive PNIPAAm-based hydrogels is to modulate its LCST to around body
temperature and preferably up to 42–43
C, a temperature used for hyperthermia
treatment of cancer [209]. But, there is a issue with PNIPAAm in that it is not
biodegradable. Therefore, PNIPAAm gel particle surfaces need to be modified or
conjugated with some other biodegradable polymers in order to develop biodegradable DDSs [210]. In an attempt, Jaiswal et al. [211] demonstrated the synthesis and
characterization of temperature-optimized and magnetically modalized PNIPAAm–
chitosan-based nanohydrogels for possible application in hyperthermia for cancer
treatment. The particle size analysis data showed that the room temperature hydrodynamic diameters for all the hydrogel particles synthesized in different weight
proportions of NIPAAm and chitosan were in the size range of 100–300 nm.
The SEM and AFM micrographs of nanohydrogels and magnetic nanohydrogels
showed that there was a reasonable decrease in hydrogel size with an increase in the
chitosan to NIPAAm ratio, which was consistent with the hydrodynamic diameter
measurements obtained by DLS. This decrement might be attributed either to
the crosslinking of chitosan to PNIPAAm or due to its role as a surfactant, or both
[212, 213]. The observed change in LCST was attributed to hydrophilic modifications
of PNIPAAm by water-soluble N,N
0 -methylene-bis-acrylamide (MBAAm) [213]
and it was conceived that the associated shift in LCST was due to a decrease in
mobility of water molecules trapped in crosslinked chain pores, defined as bound
water molecules [214, 215]. Upon reduction in hydrogel size, pores of the mesh
diminish in size and, in turn, bound water volume decreases. But, they are held there
for a longer time with respect to temperature and that requires a higher amount of heat
energy to expel them. Consequently, the LCST shifted in an upward direction. So, it
118
J. Dutta