Hydrogels: Biomaterials for Sustained and Localized Drug Delivery
237
One crucial feature of HNCs is its ability to surpass the immune system due
to its nanoscale structures and, in some cases, of the blood-brain barrier itself. It
is conceptualized by the Enhanced Permeability and Retention (EPR) mechanism
using nanocarriers [2].
5.3.1 pH-Responsive Hydrogel for Drug Delivery
pH variation is observed in body tissues and cellular compartments. For instance,
blood has pH in the range of 7.35–7.45; stomach 1.0–3.0; and duodenum 4.8–8.2
[6]. This difference in pH is exploited in formulating localized and sustained drug
release in the intended areas in response to the specific substrates. The pH-sensitive
hydrogel comprises of ionizable weak acids or a base is an attribute of the pendant
groups of the polymeric unit. Hydrogel with numerous acidic groups is referred
to as polyanions or polyacids, while the polymers with basic units are polybases or
polycations [97]. Polycations, at basic pH, deprotonate and in the acidic environment,
becomes positively charged. Combinational usages of nanocarriers that target and
accumulate at the intended site and act as a localized drug storehouse embedded
with drug are employed to design pH-sensitive hydrogel. It is the charge density
of the acidic or basic polymer backbone of the polymer that induces pH-dependent
swelling and deswelling of the hydrogel. Nanoparticles of poly β-amino ester (PbAE)
were prepared to increase of biocompatibility and pH sensitivity, for paclitaxel drug
delivery [180]. Another pH and temperature-sensitive HNC designed for treating
breast cancer using poly ε-caprolactone (PCL) for tamoxifen drug delivery. It is
channeled towards the estrogen receptor (ER) for targeted drug delivery [27]. The
degree of a pH-responsive polymer depends upon the level of ionization, protonation,
and deprotonation caused in response to its surroundings, as shown in Fig. 11 [129].
After completion of drug delivery, the degradation of the hydrogel is a mandatory
requirement for clearance from the host system. It is achieved by cleaving the polymer
backbone using hydrolysis or enzyme action [92]. Many drug delivery applications
that involve drug entrapped pH-sensitive nanogels as a carrier have been reported,
namely as anti-cancer doxorubicin, antibacterial tetracycline [218]. PLGA- Chitosanbased nanogel coated with eucalyptus oil is encapsulated with 5-fluorouracil (5-FU)
by the ‘solvent evaporation emulsification’ process for prolonged drug release for
skin cancer therapy [161].
5.3.2 Temperature Responsive Hydrogel for Drug Delivery
Polymers that exhibit sol-gel transition in response to the temperature alteration are
one of the most widely studied physical stimuli responsive ESPs. Homogenous solutions of polymers that show temperature sensitivity at critical solution temperature
(CST) are separated into polymer-rich and polymer-lean phase. When the polymer
solution reaches CST, an alteration occurs between hydrophilic and hydrophobic
chains of the polymer in an aqueous solvent. Phase diagram of the polymer/solvent
237
One crucial feature of HNCs is its ability to surpass the immune system due
to its nanoscale structures and, in some cases, of the blood-brain barrier itself. It
is conceptualized by the Enhanced Permeability and Retention (EPR) mechanism
using nanocarriers [2].
5.3.1 pH-Responsive Hydrogel for Drug Delivery
pH variation is observed in body tissues and cellular compartments. For instance,
blood has pH in the range of 7.35–7.45; stomach 1.0–3.0; and duodenum 4.8–8.2
[6]. This difference in pH is exploited in formulating localized and sustained drug
release in the intended areas in response to the specific substrates. The pH-sensitive
hydrogel comprises of ionizable weak acids or a base is an attribute of the pendant
groups of the polymeric unit. Hydrogel with numerous acidic groups is referred
to as polyanions or polyacids, while the polymers with basic units are polybases or
polycations [97]. Polycations, at basic pH, deprotonate and in the acidic environment,
becomes positively charged. Combinational usages of nanocarriers that target and
accumulate at the intended site and act as a localized drug storehouse embedded
with drug are employed to design pH-sensitive hydrogel. It is the charge density
of the acidic or basic polymer backbone of the polymer that induces pH-dependent
swelling and deswelling of the hydrogel. Nanoparticles of poly β-amino ester (PbAE)
were prepared to increase of biocompatibility and pH sensitivity, for paclitaxel drug
delivery [180]. Another pH and temperature-sensitive HNC designed for treating
breast cancer using poly ε-caprolactone (PCL) for tamoxifen drug delivery. It is
channeled towards the estrogen receptor (ER) for targeted drug delivery [27]. The
degree of a pH-responsive polymer depends upon the level of ionization, protonation,
and deprotonation caused in response to its surroundings, as shown in Fig. 11 [129].
After completion of drug delivery, the degradation of the hydrogel is a mandatory
requirement for clearance from the host system. It is achieved by cleaving the polymer
backbone using hydrolysis or enzyme action [92]. Many drug delivery applications
that involve drug entrapped pH-sensitive nanogels as a carrier have been reported,
namely as anti-cancer doxorubicin, antibacterial tetracycline [218]. PLGA- Chitosanbased nanogel coated with eucalyptus oil is encapsulated with 5-fluorouracil (5-FU)
by the ‘solvent evaporation emulsification’ process for prolonged drug release for
skin cancer therapy [161].
5.3.2 Temperature Responsive Hydrogel for Drug Delivery
Polymers that exhibit sol-gel transition in response to the temperature alteration are
one of the most widely studied physical stimuli responsive ESPs. Homogenous solutions of polymers that show temperature sensitivity at critical solution temperature
(CST) are separated into polymer-rich and polymer-lean phase. When the polymer
solution reaches CST, an alteration occurs between hydrophilic and hydrophobic
chains of the polymer in an aqueous solvent. Phase diagram of the polymer/solvent