Shell-crosslinked Pluronic L121 micelles as a drug delivery vehicle

Pluronic block copolymers (PBCs) have been shown to reverse multidrug resistance (MDR) by inhibiting the P-glycoprotein (P-gp) pump in cancer cells. One of the problems encountered with the use of PBCs is that the micelles disassociate at low concentrations. The study focused on the stabilization of PBC L121 micelles by the formation of crosslinks within their outer shells. To form crosslinks, the two terminal alcohols on L121 were first chemically converted into aldehydes (L121-CHO) using the Dess-Martin periodinane. Diamine compounds were then used to bridge the converted aldehyde termini on L121-CHO via conjugated Schiff bases. After crosslinking, the morphology of the L121 micelles remained spherical in shape and the mean particle sizes of the micelles before and after crosslinking were comparable (100 nm). After exposure of MDR KBv cells to free rhodamine-123 (R123), the accumulation of 8123 in cells was limited due to the function of P-gp. In contrast, crosslinking of L121 micelles within their outer shells significantly reduced their critical micelle concentration and greatly enhanced their stability, while maintaining their ability to inhibit P-gp function in resistant cells. The results indicated that the L121 micelles with shell crosslinks may be useful as a drug delivery vehicle for cancer chemotherapy. (c) 2006 Elsevier Ltd. All rights reserved.