Design and Synthesis of Thermo-pH Responsive OEG-based Nanogels

MACCHIONE, MICAELA A.; DARIANA ARISTIZÁBAL BEDOYA; STRUMIA, MIRIAM C.

virtual

Simposio; Virtual Internacional Symposium on Nano-/Microgels; 2020

Stimuli-responsive nanogels (NGs) are three-dimensional-crosslinked nanosized polymeric matrixes which are capable of undergoing reversible, physical or chemical changes in their properties as a consequence of environmental variations. These nanodevices are promising materials for applications in nanomedicine due to their unique properties as stimuli-responsive nature, high drug-loading capacity, protection of the entrapped drug and drug controlled release.Among the available building blocks, poly(ethylene glycol) and its derivatives exhibit thermosensitive nature with a tunable phase transition temperature (TPT) as well as excellent biocompatibility. Otherwise, mesoporous silica nanoparticles (MSNs) are interesting platforms for medical applications since they are biocompatible, have an effective cellular uptake and the morphology of the pores can be controlled providing the possibility of loading/release of different drugs. However, in bare MSNs systems, drug release takes place by diffusion immediately after administration. Thereby, the modification of the surface of MSNs with stimuli-responsive polymers giving hybrid NGs (HNGs) allows to increase the specificity of the release.In this work, we present the design and synthesis of thermo-pH responsive ethylene glycol (OEG)-based NGs and HNGs (MSN-OEG) employing a free radical dispersion/precipitation polymerization assisted by ultrasonication approach, previously reported [1]. SamplesDEGMA:OEGMAAA/IAAve. Size 25ºC (nm)PDIZ Pot. (mV)TPT (ºC)NG08:2-392.80.256-2.740.0NG1-4AA8:24% AA236.40.117-17.049.9NG2-4IA NG5-4IA8:24% AI345.20.101-14.039.5Table 1. Average size (average hydrodynamic diameter from Dynamic Light Scattering (DLS) intensity distribution), polydispersity index (PDI), Zeta potential and TPT values in aqueous solution for OEG-based NGs synthetized. DEGMA: di(ethylene glycol) methyl ether methacrylate; OEGMA: oligo(ethylene glycol) methacrylate; AA: acrylic acid; IA: itaconic acid (IA); TEGDMA: tetraethylene glycol dimethacrylate. NG0 (DEGMA-co-OEGMA) has an average size of 392.8 nm with a PDI>0.2 while NG1-4AA and NG2-4IA with 4 % of AA/IA, respectively, have lower sizes with lower PDI indicating more grade of monodispersity. A general trend that could be observed is that as the AA/IA concentration is increased (8, 12%), the size of NGs increases until size is beyond nanoscale and the corresponding PDI values result slightly higher (data not shown). These parameters indicate that the swelling grade of NGs gets higher because of the rise of the hydrophilicity of the final matrix. Zeta potential is negative in all samples, and its absolute value increases with the concentration of AA/IA as it was expected due to the incorporation of acidic groups. Comparison of the TPT of the basic polymer NG0 with that obtained for NG1-4AA indicates that TPT increases when the concentration of AA in the matrix is raised. This agrees with the prediction of obtaining higher TPT with the increase of the concentration of hydrophilic monomer in the final structure [2]. Otherwise, when 4% of IA is used, TPT is similar to the one obtained by NG0 without the acid monomer. At these conditions, acid groups of IA can form intramolecular hydrogen bonding between them that may act as hydrophobic arrangements in which polymer?polymer interactions prevail on the polymer?water ones, leading to a TPT lower than expected [3]. Otherwise, NG2-4IA showed pH-responsive behavior by exhibiting the variation of size at different pHs (data not shown). SamplesIA (%)Ave. Size 25ºC (nm)PDIZ Pot. (mV)HNG0-128.80.060Not measuredHNG1-44143.90.186-22.5HNG2-88268.20.200-28.5HNG3-1212365.70.358-30.7Table 2. Average size, PDI and Zeta potential in aqueous solution for HNGs synthetized. DEGMA and 0.25 mg of MSNs were used in the synthesis. For the synthesis of HNGs, first the silanization reaction of the MSNs to obtain MSNs@polimerizable group was performed, followed by polymerization. Nanometric sizes, negative charges and acceptable PDIs were also obtained when incorporating MSNs to the matrix. Sizes get higher as the amount of IA is increased, a trend similar to NGs without the inorganic component. However, the incorporation of 12% of IA still gives nanometric sized HNGs with negative Zeta potential. The HNGs show TPT ranging between 23 and 38ºC depending on the IA concentrations used (data not shown). All in, these results show that by changing the composition of monomers one can modulate the main important properties of NGs as size, TPT, pH responsiveness and surface charges.We acknowledge the support from Program BID-FONCyT, SECYT-UNC and CONICET.