Isocyanate-terminated Lactic Acid Oligomers as a New Means to Conjugate Functional Drugs or Polymers with Bioresorbable Hydrophobic Segments

Abstract

The use of poly(lactic acid) with activated chain ends is an alternative strategy to polymerizing lactides using coordination-insertion polymerizations in the presence of alcohols or amines when one wants to create a macromolecular prodrug or to create self-assembling amphiphilic polymers or to modify a surface. A new route to functionalized poly(a-hydroxy acid) end groups is described based on successive reactions; the activation of chain ends via the formation of a mixed anhydride, the conversion to azide, and finally the formation of isocyanate by the Curtius rearrangement, all in one pot. The various stages are monitored using FTIR spectrometry. To exemplify the potential of the method, activated lactic acid oligomers are reacted with model alcohols and amine-bearing small molecules that are bound via carbamate or urea bonds, respectively. FTIR, ¹H NMR, and SEC with a refractometric/photo diode array or refractometric/ fluorimetric double detections are used to assess the binding of the drug model on oligomers. Based on the results, the method is easily applied to small molecules, macromolecules, and surfaces bearing chemical functional groups that react with isocyanate.