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Temperature-Responsive Poly(N‑Isopropylacrylamide) Nanogels: The Role of Hollow Cavities and Different Shell Cross-Linking Densities on Doxorubicin Loading and Release
journal contribution
posted on 2020-03-04, 21:03 authored by Sakineh Hajebi, Amin Abdollahi, Hossein Roghani-Mamaqani, Mehdi Salami-KalajahiSmart
polymers with extraordinary characteristics are studied in
drug-delivery applications. In the current study, temperature-responsive
hybrid core–shell nanoparticles were synthesized by precipitation
polymerization of N-isopropylacrylamide and vinyl-modified
silica nanoparticles. These temperature-responsive hybrid core–shells
were prepared with different cross-linking densities by using 2, 4,
and 8 mol % of N,N-methylene bisacrylamide
(MBA). Hydrolysis of the silica cores of the hybrid core–shells
resulted in hollow poly(N-isopropylacrylamide) (PNIPAM)
nanogels. Functionalization of silica nanoparticles with vinyl-containing
silane modifier of 3-(trimethoxysilyl) propyl methacrylate (MPS) in
two different contents was proven by Fourier transform infrared spectroscopy.
Preparation of the hybrid PNIPAM nanogels and etching of the silica
cores were studied using thermogravimetric analysis and also electron
microscopy imaging. Sensitivity of the PNIPAM nanogel samples to temperature
was studied using ultraviolet–visible (UV–vis) spectroscopy.
In addition, dynamic light scattering was used for investigation of
the squeezing and expansion of the hybrid and hollow samples against
variation of temperature. The UV–vis spectroscopy results display
higher absorption intensities in higher contents of MPS modifier and
MBA cross-linker. The swelling content of the nanogels with hollow
cavities was higher than that of the hybrid samples. The hybrid nanogels
with 2 and 8 wt % silica content and different cross-linking densities
and also their hollow nanoparticles were used for loading and release
of doxorubicin (DOX). The release characteristics of the DOX-loaded
nanogels were studied at different temperatures using UV–vis
spectroscopy. The DOX release was higher at temperatures lower than
the gel collapse temperature of the PNIPAM network. Although the nanogels
with hollow cavities displayed higher loading capacities, the release
percentage was higher for the hybrid PNIPAM nanogels, which was confirmed
by the experimental release profiles and mathematical models. The
most appropriate fitting of the DOX release data from the PNIPAM nanogel
samples was observed for the Korsmeyer–Peppas model. Cytotoxicity
studies on HeLa cell line showed that drug-loaded hollow samples showed
higher toxicity due to loading of a higher amount of DOX.
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Keywords
vinyl-containing silane modifierRelease Smart polymerssilica coresgel collapse temperaturevinyl-modified silica nanoparticlesPNIPAM nanogelscontentUVMPSHeLa cell linespectroscopycross-linking densitiesDifferent Shell Cross-Linking DensitiesMBADOX release dataPNIPAM nanogel sampleselectron microscopy imaging
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