T HERMORESPONSIVE
DELIVERY
hyperthermia ( 42°C to 44°C) and
chemotherapeutic agents (systemically). This
combinition frequently results in increased
cytotoxicity due to a lack of target-specific
drug release from the systemically
administered dosage form. 8, 9 But the efficacy
of this bimodality approach could be increased
significantly if the chemotherapeutic agents are
delivered selectively to tumor cells along with a
thermoresponsive micro/nanocarier followed by
the application of localized hyperthermia.
Attempts have already been made to coat anti-cancer drugs into thermosensetive
nanoparticulate polymers. 10 The main
hypothesis behind such an attempt is that if the
thermoresponsive nanoparticles carrying
anticancer drugs are stable and soluble in the
blood at a normal physiologic temperature, but
releases the drug content at elevated
temperature (around 40°C to 45°C) because of
localized hyperthermia, then such a system can
improve the specificity of the drug delivery,
while reducing or minimizing systemic side
effects. So the question remains: do we have
any such smart thermosensetive carriers that
can respond to a thermal stimulus and show an
ideal phase inversion in such a temperature
range and deliver the therapeutic moiety at the
target site only?
HOW THERMORESPONSIVE DRUG
DELIVERY SYSTEMS WORK
The key feature of thermosensetive
polymers is that they exhibit a conformational
or phase transition at certain temperatures that
result in the polymer transitioning from a
soluble to insoluble form in a given solvent.
The temperature at which the transition occurs
is referred to as the critical solution
temperature. Polymers that exhibit this
behavior fall into two categories. The first
exhibits lower critical solution temperature
(LCST), in which the polymer is in solution
below the LCST and insoluble above it. 11 The
second type exhibits upper critical solution
temperature (UCST), in which the polymer is
soluble above and insoluble below the UCST in
FIGURE 2
Schematic Illustration of the Novel Thermoresponsive Drug Delivery System to Give a Drug Release
Modulated by External Temperature at the Heated Tumor Region
a given solvent. A thermosensetive polymer
that is designed for human use should have an
LCST temperature at around 41°C to 45°C
because it is near the heated tumor’s
temperature. Therefore, when a
thermosensetive polymeric carrier containing
anticancer drug passing through a heated tumor
region precipitates and shows a phase
inversion, it results in drug release at the tumor
region.
THERMODYNAMIC
CONSEQUENCES OF PHASE
TRANSITION AT LCST FOR A
POLYMER IN SOLUTION
LCST is the temperature below which a
polymer is in a solution state and above which
becomes insoluble in a given solvent. The
principles of this phenomenon can be
explained stepwise by the following:
• Generally, thermoresponsive polymers
have a hydrophilic and hydrophobic
group in their structure.
• Below the LCST, hydrophilic groups of
the polymer are hydrated due to
hydrogen bonding between the water
and polymer to form a gelatinous
structure. The hydration results in a
negative energy term (the H of
hydration). It also results in a loss of
entropy due to the ordered arrangement
of the hydrating water molecules ( S of
hydration).
• The aforementioned hydrated gelatinous
structure is hydrophilic. However, for
some polymers, if the water leaves the
structure (dehydration) for any reason,
the polymer will undergo configuration
changes in which the hydrophobic
groups predominate. For these
