A smart micellar system with an amine-containing polycarbonate shell

The present paper reports the design and preparation of an amphiphilic triblock co-polymer poly(ε-caprolactone) (PCL)–poly(6,14-dimethyl-1,3,9,11-tetraoxa-6,14-diaza-cyclohexadecane-2,10-dione) (PADMC)–PCL and the use of micelles composed of them as carriers for pH-sensitive drug release. The triblock co-polymers were synthesized via two-step ring-opening polymerization with catalysis by Novozym-435 lipase. By adjusting the feed ratio, three co-polymers with different PCL lengths and the same PADMC length were produced. The block structure of the co-polymers obtained was confirmed by comparative studies on PCL–PADMC–PCLs and the corresponding random poly(ε-caprolactone-random-6,14-dimethyl-1,3,9,11-tetraoxa-6,14-diaza-cyclohexadecane-2,10-dione) (poly(CL-r-ADMC)) by means of nuclear magnetic resonance and differential scanning calorimetry. Cell cytotoxicity tests showed that the co-polymer displayed no apparent cytotoxicity to 293T and HeLa cells. Transmissions electron microscopy indicates that the self-assembled micelles exhibited a well-defined spherical shape with a diameter between ∼30 and 50 nm. The critical aggregation concentration was dependent on the block composition. Due to the presence of ionizable tertiary amine groups in the PADMC block, acid-induced variation in the micellar morphology was evident with respect to micelle size and size distribution. The size–pH curve was characterized by a smooth sigmoid form, and had a dramatic upward shift with decreasing pH from 6.5 to 4.5, which correlated well with the buffer range of hydrophilic PADMC. As a demonstration of the potential of PCL–PADMC–PCL micelles to control drug delivery, acid induced drug release for prednisone acetate-loaded micelles was explored. PCL–PADMC–PCL micelles show good promise as smart drug carriers, sensing the local specific pH decrease around lesion sites.