Proteomics - Challenges in Delivery of Therapeutic Genomics and Proteomics - page 393

release from the system mainly by mechanisms like syneresis of fluid phase from the
gel leading to release of the entrapped drug, electrophoretic migration of the drug
toward the charged electrode, or erosion of polymeric micelles.
8.3.2 Thermo-Responsive Pulsatile/Triggered Release System
Polymers that exhibit thermosensitive and thermoreversible properties have been
studied for this purpose. The external stimuli that trigger drug release from such sys-
tems are mainly fluctuations in temperature. Often during a pathological condition,
body temperature deviates from normal (37°C), especially in fever and hyperpyrexic
conditions. These prevalent body conditions are used to trigger thermosensitive pul-
satile systems to release the stored drug. Physicochemical properties of polymers like
glass transition temperature, crystallinity, and swelling index are harnessed to achieve
the goal. Gels that undergo thermoreversible changes are called thermoresponsive
gels. The affinity of hydrogels for water results in swelling of these materials at
temperatures below the transition temperature and syneresis due to water removal
at temperatures above transition temperature, thereby releasing the solubilized drug.
Poly ( N -isopropylacrylamide)-PINPA gels have been widely used. Kaneko [24]
and Sershen et al. [25] have used gold-based photostimulated devices that absorb
radiations from the near-infrared region and transfer heat to the local microenvi-
ronment, triggering drug release from thermosensitive hydrogels. Scientists have
studied pulsatile release of insulin from gold nanoshells embedded in NIPAAm- co -
acrylamide hydrogels.
In the same vein, reverse thermoresponsive gels have also been studied. The work-
ing principle of reverse thermoresponsive gels is based on an increase in viscosity
with rise in temperature. Several patents have been filed regarding the use of PLGA
and Pluronics for reverse thermoresponsive gel formulations.
8.3.3 Electroresponsive Pulsatile/Triggered Release Systems
Electroresponsive gels prepared using oppositely charged polyelectrolytes have
also been extensively researched. The electrically responsive gels resulting out of
these polyelectrolytes undergo syneresis upon application of an electric field, trig-
gering drug release. The polyelectrolytes used in this case are principally oppositely
charged. Kwon [26] synthesized hydrogels using polycationic polyamine with poly-
anionic heparin. The hydrogels were formed when aqueous solutions containing
both of the oppositely charged polymers were mixed. The underlying mechanism
for hydrogel formation may involve ionic interaction of hydrogen bonding between
oppositely charged polyelectrolytes over a certain pH range. A complex was formed
between positively charged NH 3  and negatively charged carboxylate or sulfonate
groups of the second poly electrolyte at a pH range of 3-10.
The mechanisms underlying the triggering of drug release from such polyamino acid
or polyelectrolyte-based hydrogel devices may be described as follows: (1) augmented
membrane permeability, (2) swelling of polymers facilitating water uptake, followed by
subsequent release of stored drug, and (3) ion exchange based on concentration gradient.