Polylactide-poly(ethylene glycol) micellar-like particles as potential drug carriers: Production, colloidal properties and biological performance

The micellar-like particle systems produced from poly-D,L-lactide-poly(ethy lene glycol) (PLA-PEG) copolymers have been assessed using a range of physi cochemical characterisation methods, followed by in vivo studies of their b iodistribution after intravenous administration to the rat. The size of the PEG chain was kept constant at 5 or 2 kDa, while the PLA size increased wi thin a series from 2 to 25 kDa. The results obtained reveal, that in an aqu eous medium the copolymers assembled into micellar-like structures, with th e PLA segments forming the core and the PEG segments the surrounding corona . The size of the PLA segments dominated the process of assembly of the mol ecules and the characteristics of the resultant micellar-like particles. Th e PLA-PEG micellar particles were found to be less dynamic than those obtai ned from conventional surfactants. Particles formed from the lower molecula r weight PLA polymers allowed a level of chain mobility while the cores of the micellar particles formed from higher molecular weight PLA appeared to be solid-like in nature. The size of the micellar particles was dependent o n the copolymer molecular weight and the z-average diameter increased from 25 to 76 mn as the molecular weight of the PLA moiety increased. Ms provide s an ability to control the particle size by adjusting the molecular weight of the PLA moiety. Following intravenous administration to the rat model, micellar-like particles smaller than approximately 70 mr. accumulated in th e liver, despite the fact that the PEG corona provided an effective steric stabilization effect. Micellar-like particles with a diameter of more than approximately 70 mn exhibited prolonged systemic circulation and reduced li ver uptake, although the steric stabilisation of these particles was shown to be less effective. These findings agree with recent observations from ot her research groups; that indicate a possibility that very small particulat es can pass through the sinusoidal fenestrations in the liver and gain acce ss to the parenchymal cells of the liver.