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

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.