Candida antarctica lipase B (CALB) was found to be highly tolerant toward tertiary amino functional groups during polyester synthesis. Thus, different types of copolyesters bearing tertiary amino moieties have been successfully prepared in one step without protection and deprotection of the amines using CALB as the transesterification catalyst. Polycondensation between C4-C12 diesters (i.e., from succinate to dodecanedioate) and diethanolamine comonomers with either an alkyl (methyl, ethyl, n-butyl, t-butyl) or an aryl (phenyl) substituent on the nitrogen led to the formation of various poly(amine-co-esters). The hydrophobicity and nitrogen (or charge) density of the poly(amine-co-esters), which are crucial for gene delivery applications, can be adjusted by additionally incorporating lactone units into the copolymer chains. For this purpose, lactones with different ring size (C6-C16), diethyl sebacate (DES), and N-methyldiethanolamine (MDEA) were copolymerized to form poly(amine-co-ester) terpolymers with a wide range of lactone unit contents (10-80 mol%). A number of these amino-bearing copolyesters exhibited exceedingly high gene transfection efficiency; in particular, ?-pentadecalactone-DES-MDEA terpolymer was remarkably effective in delivering therapeutic genes to inhibit tumor growth in mice in vivo. Finally, poly(lactone-co-�-amino ester) copolymers were synthesized via ring-opening and polycondensation of ?-pentadecalactone with ethyl 3-(4-(hydroxymethyl)piperidin-1-yl)propanoate. Details regarding the synthesis of these copolymers will be reported.

Lipase-catalyzed synthesis of poly(amine-co-esters) and poly(lactone-co-beta-amino esters)

244th National Meeting (2012)

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