Hydrophilic polycarbonates: Promising degradable alternatives to poly(ethylene glycol)-based stealth materials

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Poly(ethylene glycol) (PEG) represents the gold standard for stealth polymers in polymer-based therapeutic delivery. Unfortunately, PEG has some limitations which warrant the examination of alternative polymers. High molecular weight PEG (>40 kDa) can accumulate in tissue, and in some patients, PEG can provoke an immunological response and/or an accelerated blood clearance upon repeated exposure. As an alternative to PEG, water-soluble, nonfouling polycarbonates have been developed. These hydrophilic polycarbonates, prepared by acid-catalyzed ring-opening polymerization, contain hydroxyl groups attached to the polymer side chain via an amide linkage. These materials offer an enzymatically and hydrolytically degradable alternative to PEG. The results of cell viability studies and LD50 studies indicate that these materials have minimal toxicity. Nonfouling behavior and the ability to resist/reduce aggregation with proteins were demonstrated. Diblock copolymers were also synthesized to demonstrate that these polymers can be utilized for micellar drug delivery systems.