New micelle-like polymer aggregates made from PEI-PLGA diblock copolymers: micellar characteristics and cellular uptake.

New amphiphilic block copolymers based on oligomeric polyethylenimine and poly(D,L-lactide-co-glycolide) (PEI-PLGA) were synthesized by directly coupling PLGA with a carboxyl terminal group to PEI. The block copolymers were prepared by varying the length of the hydrophobic PLGA block (M(n)=6, 10, and 21K), while that of the hydrophilic PEI block (M(n)=423) was fixed. PEI-PLGA block copolymers were found to be self-assembled in water by using a PLGA segment as a hydrophobic aggregate block and a PEI segment as a hydrophilic corona-forming block. The block copolymers formed micelle-like aggregates with critical association concentration (cac) in the range of 1.54-2.57x10(-3)g/l in water. It was found that the size and cac of the aggregates depended on the hydrophobic block length and the ionic state of the PEI block. The aggregate size decreased and the cac increased, when the PLGA block length decreased and the PEI block was protonated. As a general program aimed at the development of a new nanoscopic drug carrier, the cellular uptake behavior of PEI-PLGA aggregates was compared with that of plain PLGA nanoparticles by using confocal microscopy. The results showed that PEI-PLGA aggregates was readily adsorbed onto the cell surfaces and translocated into the cytoplasm, implying their versatile applicability as a drug carrier.