Langmuir, Vol.19, No.20, 8428-8435, 2003
Core-shell structure of PLA-PEG nanoparticles used for drug delivery
Small-angle neutron scattering (SANS) has been used to study the internal structure of poly(lactic acid)-poly(ethylene glycol) (PLA(d)-PEG) block copolymer assemblies, which are being investigated as particulate drug carriers. Three PLA(d)-PEG copolymers with a fixed PEG of 5 kDa and a fully deuterated PLA(d) block of either 3, 15 or 45 kDa were synthesized by the ring opening polymerization of d(8)-D,L-lactide, using stannous octoate as a catalyst. These copolymers assembled to form nanoparticles in aqueous media, following precipitation from a water miscible organic solvent. The hydrodynamic radius of the PLA(d)-PEG nanoparticles increased with the molecular weight of the PLA(d) block. SANS data obtained at three different solvent contrasts were analyzed simultaneously using core-shell models, which assumed a homogeneous core of uniform scattering length density and a simple functional form for the scattering length density profile of the shell. The thickness and structure of the stabilizing PEG layer were found to depend on the molecular weight of the PLA(d) block. The splayed PEG chains of the PLA(d)-PEG 3:5 assemblies were characteristic of those found in polymeric micelles. However, as the molecular weight of the PLA(d) block was increased, the PEG brush became more radially homogeneous, in accord with recent Scheutjens-Fleer mean-field theory predictions.