Smart ethylene glycol-based nanogels

CARLOS GUERRERO-BELTRÁN; MICAELA A. MACCHIONE; MIRIAM STRUMIA; MA. ÁNGELES MUÑOZ FERNÁNDEZ

Mar del Plata

Simposio; XVI Simposio Latinoamericano de Polímeros (SLAP) - XIV Congreso Iberoamericano de Polímeros.; 2018

INTEMA (UNMdP-CONICET), Mar del Plata, Argentina

INTRODUCTIONNanogels (NGs) are three-dimensional-crosslinked nanosized polymeric matrixes1. In recent decades, NGs have been widely investigated due to their unique properties as stimuli-responsive nature, high drug-loading capacity, physical stability, versatile design, stability of the entrapped drug, and controlled release of the anti-inflammatory, antimicrobial, protein, peptide and anticancer drugs2. In this work, we present the preparation of thermo-responsive ethylene glycol-based NGs employing a simple and reliable ultrasonication approach. EXPERIMENTAL METHODSA free radical dispersion/precipitation polymerization assisted by ultrasonication approach was performed3. We have employed di(ethylene glycol) methyl ether methacrylate (DEGMA), oligo(ethylene glycol) methacrylate (OEGMA, Mn 475 g mol-1), and acrylic acid (AA) or itaconic acid (IA) as monomers, tetraethylene glycol dimethacrylate (TEGDMA) as crosslinker, sodium dodecyl sulphate (SDS) as surfactant and sodium persulfate as radical initiator. Characterization was performed by IR spectroscopy, dynamic light scattering, and turbidimetry. Toxic effect of NGs was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-di-phenyltetrazolium bromide (MTT) assay. RESULTS AND DISCUSSIONWithout AA, the relation of monomers DEGMA:OEGMA 8:2 results in a lower critical solution temperature (LCST) around 39 ºC which is desirable for biomedical applications. Afterwards, the amount of crosslinker agent, surfactant and AA was varied. The results show that NGs? size increases with the rise of the AA%. Besides, as concentration of SDS increases or the crosslinker concentration decreases, the NGs? sizes become smaller. 4% of AA was not enough to give negative superficial charge, whereas 12 and 25% resulted in negative Z potential.AA/IA(%)TEGDMA (%)SDS (mg/ 10 mL)Size (nm)Z Pot. (mV)4 AA1.51.8195.92.012 AA1.51.81281.3-17.425 AA1.51.81192.0-17.212 AA1.53.6714.2-16.612 AA3.01.8765.4-13.512 AI3.01.8507.4-22.5Using IA in the same experimental conditions than AA, NGs with a smaller size and higher negative Z potential were obtained. The nanogels showed LCST in the range of 30-55 °C, while no pH-response was observed maybe because the main polymer backbone is made of thermo-responsive monomers. No cytotoxic effect was observed at 50 µg/mL in TZM.bl cells.CONCLUSIONThermo-responsive hydrogels were effectively synthetized by ultrasonication approach. Size and charge can be varied by changes in the synthetic parameters. COOH groups from AA can be used as a point of attachment for drugs or fluorescent probes for the study of internalization in cells.REFERENCES1. Z. Tang, C. et al., Prog. Polym. Sci., 60, 86?128,2016.2. A. J. Sivaram et al., Wiley Interdiscip. Rev. Nanomedicine Nanobiotechnology, 7, 509?533, 2015.3. C. Biglione, A. Sousa-herves, M. Menger, S. Wedepohl and M. C. Strumia, RSC Adv., 5, 15407?15413, 2015.ACKNOWLEDGMENTSThe authors thank CONICET, FONCyT and SECyT-UNC. MAM thank CONICET for her postdoctoral fellowship and CYTED for supporting her stay in Madrid, Spain.