Incorporation of Fe@Au nanoparticles into multiresponsive pNIPAM-AAc colloidal gels modulates drug uptake and release

Abstract

Here, a synthetic method has been optimized for the synthesis of thermo and pH responsive poly(N-isopropylacrylamide-co-acrylic acid) nanogels which are subsequently loaded with Cytochrome C using a modified breathing-in mechanism. Physico-chemical properties mapped using dynamic light scattering (DLS) and differential scanning calorimetry (DSC) confirm the swelling/de-swelling kinetics as reversible with a volume phase transition temperature (VPTT) of ~ 39 °C. Fe@Au nanoparticles were incorporated inside the nanogel networks 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 using a dialysis setup and monitored 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, incorporation and presence of Fe@Au nanoparticles and drug incorporation method are found to control both the drug release mechanism and kinetics. KEYWORDS ((Nanogels, core-shell nanoparticles, Volume phase transition temperature, programmed drug release, breathing-in)) Incorporation of Fe@Au nanoparticles into multiresponsive pNIPAM-AAc colloidal gels modulates drug uptake and release. Supporting Information.

The Influence of Differently Shaped Gold Nanoparticles Functionalized with NIPAM-Based Hydrogels on the Release of Cytochrome C

“…Figure 4b–e shows the changes in Uv-Vis spectra for AuNR, AuHex, AuBP, AuNM, and AuNS, respectively, upon coating with PEG (0.5 mg/mL), followed by hydrogel (3.3 mg/mL). AuNS shows a bathochromic shift from 523 to 529 nm upon coating with PEG, indicating a hydrophilic environment around the NPs, as has been reported earlier [43]. However, upon coating with hydrogel, the LSPR peak blue shifts (524 nm), likely due to absorption of water away from the NP surrounding by the hydrogel, result in a relatively water-deficient surrounding in the immediate vicinity of the NPs.…”

“…Figure 4a shows the LSPR characteristics of the different AuNPs measured using UV-Vis spectrometry. AuNS show an LSPR peak at 523 nm, characteristic of spherical particles [43], whereas the anisotropic NPs AuHex, AuBP, and AuNM had their peaks at 609, 619 and 749 nm, respectively, as previously reported by our group [42]. On the other hand, AuNR showed two distinct peaks, the first corresponding to the transverse axis (522 nm) and the second corresponding to the longitudinal axis (737 nm).…”

“…It can be observed that the anisotropic NPs show larger sizes compared to the DLS hydrodynamic sizes, while the sizes of the spherical NPs show close agreement with their hydrodynamic radius. A slight increase in the DLS size is observed due to measurements of different diameters; DLS measures the hydrodynamic radius rather than the core radius of the NPs as measured by S(T)EM, with a weak interparticle dipolar interaction among NPs causing weak interparticle coupling, or a combination, as reported previously [43].…”

A robust method to calculate the volume phase transition temperature (VPTT) for hydrogels and hybrids

“…Prior to synthesizing polymeric-inorganic nanogels, pNIPAm/ AAc nanogel was synthesized as per our previously reported work. 27 pNIPAm, AAc and BIS, with mole ratios 85%, 10% and 5% respectively, have been used. 1.6 mM of NIPAm and 90.8 mM of BIS were put directly into the reactor under nitrogen atmosphere.…”

“…Thereaer, these Fe@Au NPs were coated with PEG-SH followed by pNIPAm/AAc nanogel following the work already performed by our group. 27 Synthesis of PEGylated Fe@Au NPs was carried out following our previous work. (Cite reference of our Fe@Au paper) In a typical Fe NP synthesis protocol, 50 mL ODE and 740 mL OAm was degassed under Ar atmosphere and vigorous stirring at 120 C for 30 min.…”