Synthesis of Biodegradable Copolymers

It is highly desired to produce biodegradable polymers with the controlled structure matching specific enzyme in degradation reactions in different environments. To meet those demands, copolymers have been found as promising materials due to the unlimited possibilities of manipulating their chemical, physical, and mechanical properties through the composition of monomer units. 

In general, as chemical hydrolysis of hydrolytically unstable backbone is the prevailing mechanism for the polymer degradation, biodegradation can be achieved by synthesizing polymers that have hydrolytically unstable functional groups such as esters, anhydrides, orthoesters, imides, and amides. 

Handbook of Metathesis Vol 3 Polymer Synthesis, Second Edition. 

The living nature of ROMP catalyzed by well-defined metathesis initiators allowed the synthesis of homo and block copolymers with controlled lengths and compositions. Moreover, the introduction of well-defined and functional-group-tolerant Grubbs ruthenium initiators allowed the synthesis of polymers with biologically active molecules. 

Polymers bearing biologically active moieties can be obtained in two ways introduction into polymer chains after the ROMP, or selection of suitable functional monomers. The latter strategy is more useful, as it gives the most reproducible results and the cleanest product. A comprehensive feature article on ROMP polymer therapeutics has been published [10]. 

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Li, G., Yao, D., and Zong, M. (2008) Lipase-catalyzed synthesis of biodegradable copolymer containing malic acid units in solvent-free system. Eur. Polym.J., 44 (4), 1123-1129. 

Synthesis of Biodegradable Copolymers with Pendant Hydrophilic Functional Groups... 

Dobrzynski, P., Kasperczyk, J., 2006a. Synthesis of biodegradable copolymers with low-toxicity zirconium compounds. IV. Copolymerization of glycolide with trimethylene carbonate and 2,2-dimethyltrimethylene carbonate microstructure analysis of copolymer chains by high-resolution nuclear magnetic resonance spectroscopy. Journal of Polymer Science Part A Polymer Chemistry 44, 98—114. 

Occasionally in the synthesis of the copolymers, insoluble material is produced. This results from polymer containing blocks of polyglycolide rather than the desired random structure. Obviously, such compositions would have considerable effect on the performance of controlled release formulations utilizing those polymers. This problem is particularly evident when one is seeking to utilize the 50 50 glycolide/lactide copolymer as a biodegradable excipient. However, with carefully controlled polymerization conditions, useful 50 50 polymer is readily produced. 

Synthesis of Biodegradable Poiy(lactic acid-co-lysine) Copolymers Linked to Cell Adhesive Peptide Sequences General Procedure 27 ... 

Ahn CH, Chae SY, Bae YH, Kim SW. Synthesis of biodegradable multi-block copolymers of poly(L-lysine) and poly(ethy-lene glycol) as a non-viral gene carrier. J Contr Rel 2004 97 567-574. 

Details are given of the synthesis of biodegradable graft copolymers based on a backbone of polylactic acid grafted with short blocks of polyacrylamide. Emulsion and solution polymerisations were examined. Molecular structures were determined by proton NMR and FTIR and by DSC. Cytotoxicity tests were conducted to assess their biocompatibility. Preliminary results of their potential in controlled release technologies are reported. 17 refs. 

Nagata M, Hizakae S (2003) Synthesis and properties of biodegradable copolymers based on 4,4 -(adipoyldioxy)dicinnamic acid, 1,6-hexanediol, and poly(ethylene glycol)s. J Polym Sci A Polym Chem 41 2930-2938... 

Ouchi T, Miyazaki H, Arimura H, Tasaka F, Hamada A, Ohya Y (2002a), Synthesis of biodegradable amphiphilic AB-type diblock copolymers of lactide and depsipeptide with pendant reactive groups , J. Pol. Set Part A Polymer Chemistry, 40 (9), 1218-1225. 

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