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In the recent years, there has been an
emerging focus in the designing of various therapeutic devices for
biomedical and biological applications. A variety of chemical
compositions, structures, morphology, desired functional properties,
thermodynamic properties, stimuli response, and chemical and
physical interactions have shown significant interest in the use of
natural, synthetic, and biohybrid polymeric hydrogels for drug
delivery. In the last few decades, researchers have been mainly
focused on organically modified poly(phosphazenes) (OPZs) to develop
hybrid polymeric and organic-inorganic compounds. By understanding
these points, here in the present investigation, we developed
stimuli sensitive Hexachlorocyclotriphosphazene (HCP) based semi-IPN
hydrogels as potential devices for controlled delivery of
5-fluorouracil (5-FU), a chemotherapeutic agent. At first, we
synthesized a new vinyl monomer, that is,
mono(ethacryloyl-2-ethoxy)-pentakis(N1,N1-dimethylpropane-1,3-diamino)-cyclotriphosphazene
using HCP, 2-hydroxy ethylacrylate and propyl amine. Then the
synthesized monomer was involved in the designing of semi-IPNs
through free radical polymerization using poly(vinyl alcohol) (PVA)
as a supporting polymer backbone. The synthesized monomer was
confirmed by Fourier transform infrared (FTIR), 1H, and 13C NMR. The
structural, morphological, thermal properties, and polymer-drug
interactions of the networks were investigated by FTIR, scanning
electron microscope (SEM), thermo gravimetric analysis, and X-ray
diffraction, respectively. From the SEM images, it was observed that
the network is compact and dense. The pH and temperature
responsiveness of semi-IPNs was investigated by performing the
diffusion studies in physiological solutions ranging from pH =
1.0–10.0 and at temperatures 25oC and 37oC. The % swelling ratio is
maximum for high polymer-monomer ratio, minimum cross-linker
concentration, low pH, and at 25oC. Different network parameters (Mc
, , e and ) were investigated. The in vitro release of 5-FU was
conducted in pH = 1.2 and pH = 7.4 at 25oC and 37oC, and noticed
that the release was affected by both the pH and temperature and
also controlled by the composition of HCP monomer. Different kinetic
models were approached to drug release profiles and finally, it was
observedthat non-Fickian diffusion was involved in the release
mechanism and the data were well fitted with Higuchi square root
model. |
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Key words: Cyclotriphosphazene, Poly(vinyl alcohol),
Semi-IPN hydrogel, 5-fluorouracil, Network parameters, Controlled
drug release. |
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