PMID- 17055046 OWN - NLM STAT- MEDLINE DCOM- 20070126 LR - 20131121 IS - 0142-9612 (Print) IS - 0142-9612 (Linking) VI - 28 IP - 4 DP - 2007 Feb TI - Shell-crosslinked Pluronic L121 micelles as a drug delivery vehicle. PG - 725-34 AB - 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 (100nm). After exposure of MDR KBv cells to free rhodamine-123 (R123), the accumulation of R123 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. FAU - Yang, Ting-Fan AU - Yang TF AD - Department of Chemical Engineering/Bioengineering Program, National Tsing Hua University, Hsinchu, Taiwan 30013, ROC. FAU - Chen, Chun-Nan AU - Chen CN FAU - Chen, Mei-Chin AU - Chen MC FAU - Lai, Chien-Hsun AU - Lai CH FAU - Liang, Hsiang-Fa AU - Liang HF FAU - Sung, Hsing-Wen AU - Sung HW LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20061019 PL - Netherlands TA - Biomaterials JT - Biomaterials JID - 8100316 RN - 0 (Cross-Linking Reagents) RN - 0 (Drug Carriers) RN - 0 (Micelles) RN - 106392-12-5 (Poloxamer) RN - V10TVZ52E4 (Putrescine) SB - IM MH - Animals MH - CHO Cells MH - Cell Survival/drug effects MH - Cricetinae MH - Cross-Linking Reagents/*chemistry MH - Drug Carriers/*chemistry MH - Magnetic Resonance Spectroscopy MH - *Micelles MH - Microscopy, Electron, Transmission MH - Molecular Structure MH - Poloxamer/*chemistry/toxicity MH - Putrescine/chemistry MH - Temperature EDAT- 2006/10/24 09:00 MHDA- 2007/01/27 09:00 CRDT- 2006/10/24 09:00 PHST- 2006/08/14 00:00 [received] PHST- 2006/09/26 00:00 [accepted] PHST- 2006/10/24 09:00 [pubmed] PHST- 2007/01/27 09:00 [medline] PHST- 2006/10/24 09:00 [entrez] AID - S0142-9612(06)00845-3 [pii] AID - 10.1016/j.biomaterials.2006.09.035 [doi] PST - ppublish SO - Biomaterials. 2007 Feb;28(4):725-34. doi: 10.1016/j.biomaterials.2006.09.035. Epub 2006 Oct 19.