Colloidal stability and drug incorporation aspects of micellar-like PLA-PEG nanoparticles

The drug delivery properties of a series of poly(lactic acid)-poly(ethylene glycol) (PLA-PEG) micellar-like nanoparticles have been assessed in terms of their colloidal stability and their ability to incorporate a water soluble drug. These studies have focused on a range of PLA-PEG copolymers with a fixed PEG block (5 kDa) and a varying PLA segment (3-110 kDa). In aqueous media, these copolymers formed micellar-like assemblies following precipitation from water miscible solvents. There was a controlled increase in the particle size as the molecular weight of the PLA block nias increased. The characteristics of the PEG corona were also highly dependent on the PLA moiety. Copolymers with a low molecular weight PLA block (3-15 kDa) formed highly colloidally stable dispersions, with a complete PEG surface coverage. However, increasing the molecular weight of the PLA block resulted in significantly less colloidally stable nanoparticle dispersions, which flocculated in solvents that were significantly better than theta-solvents for the stabilising PEG chains. This can be attributed to a reduced PEG surface coverage and the probable presence of naked PLA 'patches' on the particle surface. These larger PLA-PEG nanoparticles (30:5-110:5) were found to be stabilised in the presence of serum components, which are thought to adsorb into the gaps on the particle surface and prevent flocculation. All of the dispersions were found to be stable under physiological conditions and therefore suitable for in vivo administration. A reasonable loading (3.1% w/w) of the micellar-like PLA-PEG 30:5 nanoparticles with the water soluble drug procaine hydrochloride was achieved. The incorporated drug was found to have no effect on the nanoparticle structure or recovery, which can be attributed to the micellar character of these assemblies and the presence of the stabilising PEG chains. (C) 1999 Elsevier Science B.V. All rights reserved.