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Biomedical Nanomaterials pp 17–57Cite as

Molecular Design, Synthesis, and Properties of Surface-Active Comb-Like PEG-Containing Polymers and Derived Supramolecular Structures for Drug Delivery

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Abstract

This chapter is devoted to the tailored synthesis and study of the properties of novel surface-active polymeric drug carriers containing side chains of PEG and other, including polyelectrolyte, chains for waterborne delivery systems. The strategy of synthesis of PEG-containing polymeric carriers via reactions of radical polymerization and further polymer-analogous transformations involving epoxide (so called “grafting to”) and peroxide ("grafting from") fragments of epoxide-containing polyperoxides of various composition and fine structure were developed and studied. The dependence of PEG grafting degree on the length of the blocks of GMA links in the backbone was shown. Water-soluble surfactants combining grafted side PEG and anionic polyelectrolyte chains were synthesized using polymerization initiated by the comb-like PEG-containing macro-initiator with side peroxide groups. An another promising way of “grafting through” synthesis of the comb-like polymeric drug carriers with side PEG chains via controlled polymerization of PEG methacrylate macromers in the presence of functional chain transfer agents was developed. The molecular weight characteristics, functionality, and surface activity of the developed polymers were studied using SEC and GPC techniques, FT-IR, NMR spectroscopy, and elementary analysis. The binding of water-soluble and water-insoluble anticancer drugs with PEGylated carriers via combination of different mechanisms was studied by using luminescent, RAMAN, UV-spectroscopy, and surface tension measurement techniques. Stable waterborne drug delivery systems based on the polymeric micelles loaded with water-soluble and water-insoluble drugs were developed and studied using SAXS, TEM, SEM, and DLS methods. The developed PEG-containing comb-like polymeric carriers and derived drug delivery systems were shown to be nontoxic in vitro (cell cultures) and in vivo (laboratory mice and rats). Their use enhances drug delivery to tumor cells, reduces the effective drug therapeutic dose, and offers a possibility to circumvent acquired resistance of tumor cells to drug action.

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Abbreviations

A∞:

Adsorption at water/air interface

AA:

Acrylic acid

BA:

Butyl acrylate

CGE:

Cumene glycidyl ether, 2-{[(4-isopropyl benzyl)oxi]methyl}oxirane

CMC:

Critical micelle concentration

DLS:

Dynamic light scattering

DMAEMA:

Dimethylaminoethyl methacrylate

DMM:

Dimethyl maleate

FCTA:

Functional chain transfer agents

FT-IR:

Fourier-transform infrared spectroscopy

GMA:

Glycidyl methacrylate

GPC:

Gel permeation chromatography

MP:

Monoperoxine, 1-isopropyl-3(4)-[1-(tert-butyl peroxy)-1-methylethyl] benzene

mPEG:

Poly(ethylene glycol) monomethyl ether

MWD:

Molecular weight distribution

NMR:

Nuclear magnetic resonance

NVP:

N-vinylpyrrolidone

PEG:

Polyethylene glycol

PEGMA:

Polyethylene glycol methacrylate

PNC:

Polymeric nanoscale carriers

RAMAN:

Raman spectroscopy

S0:

Limiting area occupied by surfactant molecule

SAXS:

Small-angle X-ray scattering

SEC:

Size-exclusion chromatography

SEM:

Scanning electron microscope

TEM:

Transmission electron microscopy

VEP:

5-(tert-butylperoxy)-5-methylhex-1-en-3-yne

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Acknowledgements

The authors are thankful to Prof. A.S. Voloshinovskyi and Prof. V.V. Vistovskyi (Ivan Franko National University of Lviv) for their assistance in studying the luminescence properties of the polymer complexes and Senior Researcher V.O. Glazunova (DonPTI, the NAS of Ukraine) for her help in the TEM study of polymer complexes.

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Authors and Affiliations

  1. Lviv Polytechnic National University, Lviv, Ukraine

    Nataliya Mitina, Anna Riabtseva, Olena Paiuk, Orest Hevus & Alexander Zaichenko

  2. Institute of Cell Biology of National Academy of Sciences of Ukraine, Lviv, Ukraine

    Nataliya Finiuk & Rostyslav Stoika

  3. Institute of Macromolecular Chemistry, Czech Academy of Sciences, Prague, Czech Republic

    Miroslav Slouf & Ewa Pavlova

  4. Danylo Halytsky Lviv National Medical University, Lviv, Ukraine

    Lesya Kobylinska, Roman Lesyk & Rostyslav Stoika

  5. Helmholtz-Zentrum Geesthacht (HZG): Centre for Materials and Coastal Research, Geesthacht, Germany

    Vasyl Garamus

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  1. Nataliya Mitina
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Correspondence to Alexander Zaichenko .

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  1. Head of Department of Regulation of Cell Proliferation and Apoptosis, Institute of Cell Biology, National Academy of Sciences of Ukraine, Lviv, Ukraine

    Rostyslav S. Stoika

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Mitina, N. et al. (2022). Molecular Design, Synthesis, and Properties of Surface-Active Comb-Like PEG-Containing Polymers and Derived Supramolecular Structures for Drug Delivery. In: Stoika, R.S. (eds) Biomedical Nanomaterials. Springer, Cham. https://doi.org/10.1007/978-3-030-76235-3_2

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