Polymer therapeutics: concepts and applications.
Polymer therapeutics encompass polymer-protein conjugates, drug-polymer conjugates, and supramolecular drug-delivery systems. Numerous polymer-protein conjugates with improved stability and pharmacokinetic properties have been developed, for example, by anchoring enzymes or biologically relevant proteins to polyethylene glycol components (PEGylation). Several polymer-protein conjugates have received market approval, for example the PEGylated form of adenosine deaminase. Coupling low-molecular-weight anticancer drugs to high-molecular-weight polymers through a cleavable linker is an effective method for improving the therapeutic index of clinically established agents, and the first candidates have been evaluated in clinical trials, including, N-(2-hydroxypropyl)methacrylamide conjugates of doxorubicin, camptothecin, paclitaxel, and platinum(II) complexes. Another class of polymer therapeutics are drug-delivery systems based on well-defined multivalent and dendritic polymers. These include polyanionic polymers for the inhibition of virus attachment, polycationic complexes with DNA or RNA (polyplexes), and dendritic core-shell architectures for the encapsulation of drugs. In this Review an overview of polymer therapeutics is presented with a focus on concepts and examples that characterize the salient features of the drug-delivery systems.
Haag
Rainer
R
Organic and Macromolecular Chemistry, Department of Chemistry and Biochemistry, Freie Universität Berlin, Takustrasse 3, 14195 Berlin, Germany.
Kratz
Felix
F
D000595:Amino Acid Sequence; D000818:Animals; D004337:Drug Carriers / Q000737:chemistry / Q000627:therapeutic use; D016503:Drug Delivery Systems; D015195:Drug Design; D004705:Endocytosis; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D046911:Macromolecular Substances / Q000737:chemistry / Q000627:therapeutic use; D008958:Models, Molecular; D015394:Molecular Structure; D011108:Polymers / Q000737:chemistry / Q000627:therapeutic use*; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry / Q000627:therapeutic use
D004337:Drug Carriers; D046911:Macromolecular Substances; D011108:Polymers; D011506:Proteins