Nanospheres with a smectic hydrophobic core and an amorphous PEG hydrophilic shell: structural changes and implications for drug delivery.

The structure of nanospheres with a crystalline core and an amorphous diffuse shell was investigated by small-angle neutron scattering (SANS), small-, medium-, and wide-angle X-ray scattering (SAXS, MAXS and WAXS), and differential scanning calorimetry (DSC). Nanospheres, 28 to 35 nm in diameter, were prepared from a triblock copolymer with poly(ethylene glycol) (PEG) hydrophilic end-blocks and oligomers of alternating desaminotyrosyl-tyrosine octyl ester (DTO) and suberic acid (SA) as the central hydrophobic block. In the lyophilized nanospheres, the diffraction patterns show that the PEG shell is ∼10 nm in thickness and crystalline, and the hydrophobic core is ∼10 nm in diameter with a smectic liquid crystalline texture. In aqueous dispersions, the hydrated PEG forms an amorphous shell, but the crystalline phase in the core persists at concentrations down to 1 mg ml-1 as evidenced by the sharp MAXS diffraction peak at a d-spacing of 24.4 Å and a melting endotherm at 40 °C. As the dispersion is diluted (<1 mg ml-1), the core becomes less ordered, and its diameter decreases by 50% even though the overall size of the nanosphere remains essentially unchanged. It is likely that below a critical concentration, intermixing of hydrophobic segments with the PEG segments reduces the size and the crystallinity of the core. At these concentrations, the PEG corona forms a eutectic with water. The mechanisms by which the concentration of the dispersion influences the structure of the nanospheres, and consequently their drug-release characteristics, are discussed.