Abstract
Glutathione-chitosan conjugates are adequate carriers for anticancer treatment due to their ability for inhibition of efflux pumps, improved mucoadhesivity and in-situ gelling. These conjugates were obtained via carbodiimide at different reaction times in order to get different thiolation degrees (i.e., 4.4!, 5.1! and 7.0!) and their behavior in aqueous media at a pH of 4, 5 and 6 was assessed by measurements of hydrodynamic diameter, zeta potential and rheological analyses at a pH ranging from 4 to 6. Data examination was conducted by principal component analysis (PCA) which in turn explained 73.1! of data variability. All samples showed a Newtonian flow and thiolation rendered materials with a highly pronounced temperature-dependent behavior and a gel-like structure. In turn, the phase shift angle was the most prominent rheological change especially at a pH of 5.0 and 6.0 due to the formation of disulfide bonds. The thiolation degree was the most influential factor and it was inversely related to particle charge and consistency index.
References
[1] Laffleur F., Berknop-Schnürch A., Thiomers: promising platform for macromolecular drug delivery, Futur. Med. Chem. 4, 2012, 2205–2216.10.4155/fmc.12.165Search in Google Scholar PubMed
[2] Bonegel S., Berknop-Schnürch A., Thiomers — From bench to market, J. Control. Rel. 195, 2014, 120–129.10.1016/j.jconrel.2014.06.047Search in Google Scholar PubMed
[3] Cho I.S., Cho M.O., Jang B.S., Cho J.K., Park K.H., Kang S.W., Huh K.M., Synthesis and characterization of thiolated hexanoyl glycol chitosan as a mucoadhesive thermogelling polymer, Biomater. Res. 22, 2018, 1–10.10.1186/s40824-018-0137-7Search in Google Scholar PubMed PubMed Central
[4] Sakloetsakun D., Hombach J.M., Bernkop-Schnürch A., In situ gelling properties of chitosan–thioglycolic acid conjugate in the presence of oxidizing agents, Biomaterials. 30, 2009, 6151–6157.10.1016/j.biomaterials.2009.07.060Search in Google Scholar PubMed
[5] Ciro Y., Rojas J., Salamanca C., Thiolated chitosan: A promising strategy for improving the effectiveness of antiancer drugs, In Analytical and Pharmaceutical Cheimistry, SMGroup, 2017.Search in Google Scholar
[6] Mojarradi H., Coupling of substances containing a primary amine to hyaluronan via carbodiimide-mediated amidation, 2010.Search in Google Scholar
[7] Kafedjiiski K., Föger F., Werle M., Berknkop-Schnürch A., Synthesis and in vitro evaluation of a novel chitosan-glutathione conjugate, Pharm. Res. 22, 2005, 1480–1488.10.1007/s11095-005-6248-6Search in Google Scholar PubMed
[8] Pereria A.G.B., Muniz E.C., Hsieh Y.L., 1H NMR and 1H-13C HSQC Surface Characterization of Chitosan-Chitin Sheath-Core Nanowhiskers, Carbohydr. Polym. 123, 2015, 46–52.10.1016/j.carbpol.2015.01.017Search in Google Scholar PubMed
[9] Kaiser L.G., Marjańska M., Matson G.B., Iltis I., Bush S.D., Soher B.J., Mueller S., Young K., 1H MRS detection of glycine residue of reduced glutathione in vivo, J. Magn. Reson. 202, 2010, 259–266.10.1016/j.jmr.2009.11.013Search in Google Scholar PubMed PubMed Central
[10] Li J., Shu Y., Hao T., Wang Y., Quian Y., Duan C., Sun H., Lin Q., Wang C., A chitosan-gluthathione based injectable hydrogel for suppression of oxidative stress damage in cardiomyocites, Bio-materials. 34, 2013, 9071–9081.10.1016/j.biomaterials.2013.08.031Search in Google Scholar PubMed
[11] Hussain Z., Katas H., Mohd Amin M.C., Kumolosasi E., Buang F., Sahudin S., Self-assembled polymeric nanoparticles for percutaneous co-delivery of hydrocortisone/hydroxytyrosol: An ex vivo and in vivo study using an NC/Nga mouse model, Int. J. Pharm. 444, 2013, 109–119.10.1016/j.ijpharm.2013.01.024Search in Google Scholar PubMed
[12] Saïed N., Aïder M., Zeta potential and turbidimetry analyzes for the evaluation of chitosan/phytic acid complex formation, J. Food Res. 3, 2014, 71–81.10.5539/jfr.v3n2p71Search in Google Scholar
[13] Osswald T.A., Rudolph N., Generalized Newtonian Fluid (GNF) Models. In Polymer Rheology: Fundamentals and Applications, Hanser Publishers, Munich, 2014.10.3139/9781569905234.fmSearch in Google Scholar
[14] Duffy J., Measuring the rheology of polymer solutions, 2015.Search in Google Scholar
[15] Hwang J.K., Shin H.H., Rheological properties of chitosan solutions, Korea-Australia. Rheol. J. 12, 2000, 75–179.Search in Google Scholar
[16] Singh V., Kumari K., Rheological behaviour of chitosan-starch solution, Asian. J. Chem. 25, 2013, 9817–9821.10.14233/ajchem.2013.15435Search in Google Scholar
[17] Bernkop-Scnürch A., Hornof M., Zoidl, Thiolated polymer-sthiomers: Synthesis and in vitro evaluation of chitosan-2-iminothiolane conjugates, Int. J. Pharm. 260, 2003, 229–237.10.1016/S0378-5173(03)00271-0Search in Google Scholar
[18] Hornof M.D., Kast C.E., Bernkop-Schnürch A., In vitro evaluation of the viscoelastic properties of chitosan-thioglycolic acid conjugates, Eur. J. Pharm. Biopharm. 55, 2003, 185–190.10.1016/S0939-6411(02)00162-5Search in Google Scholar
[19] Krauland A.H., Hoffer M.H., Bernkop-Schnürch A., Viscoelastic properties of a new in situ gelling thiolated chitosan conjugate, Drug. Dev. Ind. Pharm. 31, 2005, 885–893.10.1080/03639040500271985Search in Google Scholar PubMed
[20] Torres M.A., Beppu M.M., Arruda E.J., Viscous and viscoelastic properties of chitosan solutions and gels, Brazilian. J. Food. Technol. 9, 2006, 101–108.Search in Google Scholar
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