Abstract
Here, a synthetic method has been optimized for the synthesis of thermoresponsive and pH-responsive poly(N-isopropylacrylamide-co-acrylic acid) nanogels which are subsequently loaded with cytochrome C by using a modified breathing-in mechanism. Physico-chemical properties mapped by using dynamic light scattering (DLS) and differential scanning calorimetry (DSC) confirm the swelling/deswelling kinetics as reversible with a volume phase transition temperature (VPTT) of ~39 °C. Fe@Au nanoparticles were incorporated inside the nanogel networks by using two different methods: coating and in situ growth. The latter bears closer resemblance to the nanogels only, while the former follows the trend of bare Fe@Au nanoparticles. High loading (~96 %) and encapsulation (500 μg/mg of nanogels) of cytochrome C were obtained. Release experiments performed by using a dialysis set-up and monitored by using UV-vis spectroscopy show the highest release at 40 °C and pH 3.2 (high temperature, low pH), with maximum release from the Fe@Au-coated nanogels that also show a reverse swelling-collapse trend. The location of the drug, the incorporation and presence of Fe@Au nanoparticles and the drug incorporation method are found to control both the drug release mechanism and kinetics.
Highlights
Colloidal gels in the nano regime, more commonly referred to as nanogels (NGs), have attracted much attention in drug delivery applications especially for stimuli-responsive release; i.e.; release of cargo molecules under the influence of temperature, pH, ionic strength or other external parameters.[1, 2] NGs refer to swollen nanosized networks formed by physical or chemical cross-linking of hydrophilic or amphiphilic polymer chains.[3]
Polymerization occurs via homogeneous nucleation, which is initiated by the sulphate radicals generated from the initiator.[24]
Common steps of radical propagation and chain growth continue yielding critical polymer chain length. These collapse upon themselves, forming precursor particles. These collapsed particles grow by a combination of the following mechanisms viz aggregation of other precursor particles, by being captured by existing particles, by capturing growing oligoradicals and by monomer addition.[8]
Summary
Colloidal gels in the nano regime, more commonly referred to as nanogels (NGs), have attracted much attention in drug delivery applications especially for stimuli-responsive release; i.e.; release of cargo molecules under the influence of temperature, pH, ionic strength or other external parameters.[1, 2] NGs refer to swollen nanosized networks formed by physical or chemical cross-linking of hydrophilic or amphiphilic polymer chains.[3] These offer several advantages over conventional drug delivery systems such as liposomes, microspheres, cyclodextrins and so on,[4, 5] by providing a finer temporal control over drug release due to their large surface area and by allowing longer circulation times and targeting properties upon suitable functionalization. NGs have been shown to exhibit high loading and encapsulation efficiencies. Loading efficiency gives an indication of the thermodynamic distribution of the drug, it is not sufficient to indicate delivery vehicle stability against leakage. [6] In this regard, crosslinked NGs are known to provide high encapsulation stability to the drug molecule, rendering them suitable for long term use.[7]. Loading efficiency gives an indication of the thermodynamic distribution of the drug, it is not sufficient to indicate delivery vehicle stability against leakage. [6] In this regard, crosslinked NGs are known to provide high encapsulation stability to the drug molecule, rendering them suitable for long term use.[7]
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