Abstract
To overcome multidrug resistance (MDR) existing in tumor chemotherapy, polymeric micelles encoded with folic acid on the micelle surface were prepared with the encapsulation of a potent MDR modulator, FG020326. The micelles were fabricated from diblock copolymers of poly(ethylene glycol) (PEG) and biodegradable poly(ε-caprolactone) (PCL) with folate attached to the distal ends of PEG chains. The folate-conjugated copolymers, folate-PEG-PCL, were synthesized by multistep chemical reactions. First, allyl-terminated copolymer (allyl-PEG-PCL) was synthesized through a ring-opening polymerization of ε-caprolactone in bulk employing monoallyl-PEG as a macroinitiator. Second, the allyl terminal groups of copolymers were converted into primary amino groups by a radical addition reaction, followed by conjugation of the carboxylic group of folic acid. In vitro studies at 37°C demonstrated that FG020326 release from micelles at pH 5.0 was faster than that at pH 7.4. Cytotoxicity studies with MTT assays indicated that folate-functionalized and FG020326-loaded micelles resensitized the cells approximately five times more than their folate-free counterparts (p < 0.01) in human KBv200 cells treated with vincristine (VCR). The in vitro Rhodamine 123 efflux experiment using MDR KBv200 cells revealed that when cells were pretreated with folate-attached and FG020326-loaded micelles, the P-glycoprotein (P-gp) drug efflux function was significantly inhibited.
Original language | English (US) |
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Pages (from-to) | 48-60 |
Number of pages | 13 |
Journal | Journal of Biomedical Materials Research - Part A |
Volume | 86 |
Issue number | 1 |
DOIs | |
State | Published - Jul 2008 |
Keywords
- Folate functionalization
- Multidrug resistance
- Poly (ethylene glycol)-poly(ε- caprolactone)
- Polymeric micelles
- Tumor targeting
ASJC Scopus subject areas
- Ceramics and Composites
- Biomaterials
- Biomedical Engineering
- Metals and Alloys