Dendrimers as nanocarriers for nucleoside analogues

Abstract

Dendrimers constitute a class of hyperbranched macromolecules with several potential applications due to their unique properties such as a well-defined structure, multivalency and biocompatibility. These polymers became one of the most promising drug nanocarriers, providing improved solubility of therapeutics, high loading capacity and controllable biodistribution pattern. In addition, the use of dendrimers as drug delivery devices in cancer therapies may help to overcome the resistance mechanisms by transporting activated drug molecules directly to cancer cells. In the recent years, dendrimers were intensively studied for delivery of nucleoside analogues (NAs), essential elements of antiviral therapies, as well as treatments of leukemia, lymphoma and various types of solid tumors. These agents act as antimetabolites, competing with physiological nucleosides, and interacting with intracellular enzymes and nuclear acids to induce cytotoxicity. However, efficiency of NAs-based therapies is often limited by factors like fast metabolism, disadvantageous biodistribution, low solubility and various side effects. In case of treatment of leukemia, target cells usually develop drug resistance, which reduces the activity of nucleoside analogues even further. Thus, drug carrier systems are studied to improve the efficacy and specificity of action of these compounds. In this review, we summarize available data concerning the possibility of application of dendrimers as delivery devices for nucleoside analogues and their active, triphosphate forms.