Small oligomeric micelles based on end group modified mPEG-oligocaprolactone with monodisperse hydrophobic blocks

To design stable biodegradable micelles with a size smaller than 20 nm, the self-assembly of methoxypoly(ethylene glycol)-b-oligocaprolactones (mPEG-b-OCLs), and the effect of OCL block length and terminal derivatization with an aromatic group were studied. The studied oligomers consisted of an mPEG block with a molecular weight of 750 Da and a monodisperse OCL block of 1-7 units with a hydroxyl end group that was either unmodified, benzoylated or naphthoylated. They were prepared by preparative HPLC of the polydisperse block oligomers. Differential scanning calorimetry demonstrated that the two blocks were phase separated and crystallized separately. These block oligomers formed small and almost monodisperse oligomeric micelles with a hydrodynamic diameter of 8-15 nm, which could be tailored by the size of the hydrophobic block. The critical aggregation concentration (CAC) of the unmodified mPEG-b-OCLs was 0.03-4 mg/mL, and it decreased with increasing length of the OCL chain. End group modification resulted in an extensive reduction of the CAC to values as low as 0.003 mg/mL. This is expected to result in a better stability of these oligomeric micelles toward dilution upon intravenous administration, which makes these modified mPEG-b-OCLs very promising candidates for drug delivery purposes.