Study of mechanisms for increasing the biocompatibility of various substances with biological structures using polyethylene glycols using the spin probe method
Hydrophobic spin-labeled carboline and a number of spin-labeled steroids dissolve well in both pure PEG and aqueous PEG solutions, demonstrating the presence of a triplet in the EPR spectrum. It was shown that the introduction of 20% aqueous solutions of PEG mol. m. from PEG-200 to PEG-40,000, the hydrophobic spin of labeled progesterone or carboline from the hydrophobic cavity of SAB is effectively displaced into the solution of bovine serum albumin (SAB) by competing with the hydrophobic cavity of SAB. Polyethylene glycols demonstrate full biocompatibility even with hydrophobic biological structures and, as biocompatibility enhancers, are universal. Analysis of the curve of the dependence of PEG microviscosity on mol. m. shows the presence of an inflection point on the curve in the area of the pier. m. 300-400, which indicates the compaction of the structure of PEG and corresponds to published data on the partial helixing of a polyethylene glycol molecule, starting with PEG-400 and above, in which the main role is played by hydrogen bonds of the PEG molecule. Methylene hydrophobic PEG residues appear inside the polyethylene glycol helix, and the polar groups providing the PEG molecules with osmotically active properties and causing dehydration of cell membranes appear outside the PEG helix. Therefore, with the growth of mol. m. PEG ability to dehydrate cells increases. Apparently, the mechanism of increasing PEG biocompatibility is the ability of PEG molecules to compact, spiralize, or expand molecules to accept the optimal conformation of the structure, providing their hydrophobic or polar groups for optimal binding on the one hand to nanoparticles and, on the other, to a bioobject. The introduction of conjugates of PEG nanoparticles into cells, which oppositely affects the microviscosity of membranes and compensates for the negative effect of nanoparticles on membranes, is the second mechanism for increasing the biocompatibility of nanoparticles. The possibility of the interaction of PEG with nanochorns with the orientation of PEG units along the cone needles (nanotubes) of nanochorns has been shown to increase the biocompatibility of nanochorns.
Yang K., Zhang S., Zhang G., Sun X., Lee S.-T, Liu Z. Graphene in mice: ultrahigh in vivo tumor uptake and efficient photothermal therapy. Nano Lett. 2010. 10: 3318. https://doi.org/10.1021/nl100996u
Sun X., Liu Z., Welsher K., Robinson J. T., Goodwin A., Zaric S., Dai H. Nano-Graphene Oxide for Cellular Imaging and Drug Delivery. Nano Res.. 2008. 1(3): 203. https://doi.org/10.1007/s12274-008-8021-8
Liu Z., Robinson J. T., Sun X., Dai H. PEGylated nanographene oxide for delivery of water-insoluble cancer drugs. Am J. Chem. Soc. 2008. 130(33): 10876. https://doi.org/10.1021/ja803688x
Chen Y.J., Zhou S., Hou P., Yang Y. et. al. Characterization and in vitro cellular uptake of PEG coated iron oxide nano-particles as MRI contrast agent. Die Pharm. Int. J. Pharm. Sci. 2010. 36(7): 481.
Prencipe G., Tabakman S.M., Welsher K., Liu Z. et al. PEG Branched Polymer for Functionalization of Nanomaterials with Ultralong Blood Circulation. Am. Chem. Soc. 2009. 131(13): 4783. https://doi.org/10.1021/ja809086q
Romberg B., Hennink W.E., Storm G. Sheddable coating for longcirculating nanoparticles. Pharm. Res. 2008. 25: 55. https://doi.org/10.1007/s11095-007-9348-7
Vonarbourg A., Passirani C., Saulnier P., Benoit J.P. Parameters influencing the stealthiness of colloidal drug delivery systems. Biomaterials. 2006. 27: 4356. https://doi.org/10.1016/j.biomaterials.2006.03.039
Murakami T., Fan J., Yudasaka M., Iijima S., Shiba K. Solubilization of single-wall carbon nanohorns using a PEGdoxorubicin conjugate. Molecular Pharmaceutics. 2006. 3: 407. https://doi.org/10.1021/mp060027a
Lichtenstein G.I. Spin tag method in molecular biology. M.: Science. 1974. 12. [in Russian].
Berliner L. Method of spin labels. Theory and application. M.: World. 1979. 639. [in Russian].
Ivanov L.V., Lyapunov A.N., Kartel N.T., Nardid O.A., Okotrub A.V., Kirilyuk I.A., Cherkashina Y.O. Delivery of lipophilic spin probes by carbon nanotubes to red blood cells and blood plasma. Surface. 2014. 6(21) 292. [in Russian].
Ivanov L.V., Orlova I.N. Biopharmaceutical studies aimed at optimizing the composition, properties and route of administration of drugs. In Sat. "Technology and standardization of drugs". 2000. 2. 558. [in Russian].
Moiseev V.A. Molecular mechanisms of cryodamage and cryoprotection of proteins and biological membranes. Diss. for a job. student degrees b. s.: SR. 1984. 331. [in Russian].
Ivanov L.V., Kartel N.T. Characterization of the rheological properties of the surface of nanobioobjects by the method of spin probes. Surface. 2012. 4(19):334. [in Russian].
Kartel N.T., Ivanov L.V., Lyapunov A.N., Okotrub A.V., Nardid O.A., Cherkashina Ya.O., Derymedved L.V. A study of the effect of carbon nanotubes with different structure on the microviscosity and integrity of erythrocyte membranes using a spin probe method Mod. Science- Moderni. 2017. 6: 111.
Kartel N.T., Ivanov L.V., Lyapunov A.N., Nardid O.A., Cherkashina Y.O., Gurova O.A., Okotrub A.V. Evaluation of the effect of carbon nanochorns on the microviscosity of erythrocyte membranes and plasma proteins of rat blood using the spin probe method. Reports of NAS of Ukraine. 2017. 12: 73. [in Russian].
Kartel N.T., Ivanov L.V., Lyapunov A.N., Nardid O.A., Scherbak O.V., Gurova O.A. Okotrub A.V. Study of the structural features of detonation nanodiamonds and their effect on the microviscosity of rat erythrocyte membranes using the spin probe method. Surface. 2018. 10(25): 286. [in Russian].