The study of hydrophobic drug loading in Rf-PEG micelles

CHED 25

Yong Ba, yba@calstatela.edu1, Errol V. Mathias, emathia@exchange.calstatela.edu1, Yougang Mao, ymao@calstatela.edu1, Xiangli Liu, lucy2468@sbcglobal.net1, Anuja Prabhutendolkar1, and Julia A. Kornfield, jak@cheme.caltech.edu2. (1) Department of Chemistry and Biochemistry, California State University, Los Angeles, 5151 State University Drive, Los Angeles, CA 90032, (2) Division of Chemistry and Chemical Engineering, California Institute of Technology, Mail Code 210-41, Pasadena, CA 91125
Rf-PEG is functionally modified polyethylene glycol (PEG) with two hydrophobic fluoroalkyl (Rf) terminal groups. Rf-PEGs with certain middle blocks and end lengths exhibit interesting properties of sol-gel coexistence and surface erosion, which renders this hydrogel system a good candidate as a hydrophobic drug-delivery depot for controlled and sustained drug release application.

To evaluate the feasibility and loading capacity of Rf-PEG micelles for hydrophobic drug delivery, we have made an electron spin labeled hydrophobic drug, Chlorambucil-Tempol adduct ( 4-hydroxy-2, 2, 6, 6-tetramethylpiperidine-N-oxyl) (CT). Chlorambucil (Brand name: Leukeran) belongs to the nitrogen mustard group of alkylating agents. It is most commonly used to treat chronic lymphocytic leukaemia, slow growing non-Hodgkin's lymphomas, Hodgkin's disease and ovarian cancer. Tempol contains a stable nitroxide free radical with an unpaired electron primarily located in the g-orbital of the nitroxide group. The free radical gives a hyperfine triplet EPR spectrum due to its interaction with the 14N nucleus. The free radical also acts as a relaxation reagent for monitoring the drug delivery using NMR relaxation technique.

CT loaded Rf-PEG hydrogels were prepared using a sonication method and the CT's drug loading and dynamic properties in the Rf-PEG micelles were studied using variable temperature dependent EPR and 1H and 19F relaxation NMR techniques. The experimental results show that CT molecules were dominantly encapsulated in the Rf-cores of the micelles and the maximum loading capacity was also determined.

This study is supported by NSF Grant #0351848.