(197c) Polylactide-Based Biodegradable Zwitterionic Polymers and Their Conjugates with Drugs for Biomedical Applications

Authors: 
Sun, H., University at Buffalo, The State University of New York
Commisso, A., University at Buffalo, The State University of New York
Capeling, M., University at Buffalo, The State University of New York
Wu, Y., University at Buffalo, The State University of New York
Cheng, C., University at Buffalo, The State University of New York
Wang, Q., University at Buffalo, The State University of New York
Incorporating functionalities with biodegradable macromolecular architectures, functional polylactides (PLAs) have important applications in polymer-based therapeutics. In particular, the integration of functional PLAs with hydrophilic poly(ethylene glycol) (PEG) chains and other biomedical-relevant structures has generated a variety of novel biomaterials with significant application potentials in therapeutic delivery. However, reduced bioactivity and immunogenicity of PEGylated therapeutics severely restrict their biomedical efficacy. Recently zwitterionic polymers (ZPs) have attracted significant interests as alternatives to PEG due to their special properties. Several studies on integrating non-degradable ZPs with degradable polymeric structures have been reported, but the non-biodegradable ZPs still would cause side effects and systemic toxicity resulted from polymer accumulation. Therefore, it is critically important to develop biodegradable ZPs for modification of therapeutics. Herein we report fully biodegradable ZPs and the corresponding polymer-drug conjugates (PDCs). PLA-based main-chain was designed for the ZPs and the PDCs because of its biodegradability. Carboxybetaine and sulfobetaine were selected as the zwitterions because they are superhydrophilic. Clinic anticancer drugs, such as paclitaxel (PTX), were chosen as the drug moieties of the PDCs. The ZPs and PDCs were synthesized by thiol-ene reactions of thiol-functionalized zwitterions and/or drugs with allyl-functionalized PLA. These materials showed enzymatic degradability and well-suppressed nonspecific interaction with biomolecules, and the PDCs further exhibited acid-sensitive sustained drug release behavior. Moreover, cytotoxicity and cellular uptake studies illustrated high biocompatibility of the ZPs, as well as remarkable anticancer effectiveness and ready cellular internalization of the PDCs. Overall, this work indicates the promising application potentials of biodegradable ZP-based biomaterials.