Polymer Derivatives of Anticancer Drugs: Features of Synthesis and Biological Activity

The state of the development of polymeric derivatives of anticancer agents for selective delivery is assessed, and relevant directions for further development and improvement in this field are identified. As part of the work, the available data on polymeric derivatives of anticancer preparations was analyzed, and the relevant unsolved problems in this direction were determined. Polymer systems for the selective delivery of anticancer agents, such as polymer micelles, polymer conjugates, polymer complexes, and nanohydrogels, are considered. The analysis was performed with respect to first-line therapy preparations (doxorubicin, cisplatin, 5-fluorouracil). The features of the synthesis of polymer systems for selective delivery are considered. The main directions of binding of the drug to the polymer carrier are determined. The advantage of polymeric carriers is their high molecular weight, which ensures the best pharmacokinetic parameters. The use of water-soluble carriers makes it possible to obtain simple injection systems, and the presence of functional groups in the polymer chain enables the polymer to be modified with various drugs and vectors for tumor cells. Such systems may also contain components (vectors) that “recognize” tumor cells, which increases the level of specific drug interactions with the target cell. Folic acid can be such a vector, since the expression of its receptors is higher for some tumor cells than for normal ones. Another example is steroid hormone residue; there are a sufficient number of its receptors on the surface of cancer cells. These compounds, which are used as cancer cell vectors, are poorly soluble in water. These substances become chemically attached to a water-soluble polymer carrier at a specific concentration. The system then becomes water-soluble. There are practically no studies on the search for and use of carrier polymers with their own pharmacological activity, including antitumor and immunostimulating. Polymethacrylates are a class of anionic polymers with their own potential pharmacological activity, which is associated with activation of the immune system. There are promising areas of research in this field: the determination of the optimal conditions for the synthesis of a water-soluble anionic polymer carrier based on methacrylic acid with the characteristics of a given molecular weight; the determination of the cytotoxicity of potential polymeric carriers in an in vitro cell culture and of the dependence of the cytotoxic effect on the molecular-weight characteristics of the polymer; the production of polymeric conjugates of doxorubicin, 5-fluorouracil, cisplatin, and their combinations; the study of the effect of molecular-weight characteristics, the structure of the polymer chain, and the degree of chemical modification of (co)polymers on the release of drugs from the polymer system under conditions simulating biosystems and on the cytotoxicity of polymer conjugates in vitro and in vitro; and the determination of their own immunostimulating properties (the study of the activation of macrophages under the action of polymers) of polymeric carriers with respect to the molecular weight, polydispersity, and the presence of hydrophilic anionic groups.