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Synthesis and evaluation of a novel ligand for folate-mediated targeting liposomes
- Source :
-
International Journal of Pharmaceutics . May2008, Vol. 356 Issue 1/2, p29-36. 8p. - Publication Year :
- 2008
-
Abstract
- Abstract: Folate receptors (FRs) have been identified as cellular surface markers for cancer and leukemia. Liposomes containing lipophilic derivatives of folate have been shown to effectively target FR-expressing cells. Here, we report the synthesis of a novel lipophilic folate derivative, folate-polyethylene glycol-cholesterol hemisuccinate (F-PEG-CHEMS), and its evaluation as a targeting ligand for liposomal doxorubicin (L-DOX) in FR-expressing cells. Liposomes containing F-PEG-CHEMS, with a mean diameter of 120±20nm, were synthesized by polycarbonate membrane extrusion and were shown to have excellent colloidal stability. The liposomes were taken up selectively by KB cells, which overexpress FR-α. Compared to folate-PEG-cholesterol (F-PEG-Chol), which contains a carbamate linkage, F-PEG-CHEMS better retained its FR-targeting activity during prolonged storage. In addition, F-PEG-CHEMS containing liposomes loaded with DOX (F-L-DOX) showed greater cytotoxicity (IC50 =10.0μM) than non-targeted control L-DOX (IC50 =57.5μM) in KB cells. In ICR mice, both targeted and non-targeted liposomes exhibited long circulation properties, although F-L-DOX (t 1/2 =12.34h) showed more rapid plasma clearance than L-DOX (t 1/2 =17.10h). These results suggest that F-PEG-CHEMS is effective as a novel ligand for the synthesis of FR-targeted liposomes. [Copyright &y& Elsevier]
- Subjects :
- *VITAMIN B complex
*CANCER
*LEUKEMIA
*LIPOSOMES
Subjects
Details
- Language :
- English
- ISSN :
- 03785173
- Volume :
- 356
- Issue :
- 1/2
- Database :
- Academic Search Index
- Journal :
- International Journal of Pharmaceutics
- Publication Type :
- Academic Journal
- Accession number :
- 31921607
- Full Text :
- https://doi.org/10.1016/j.ijpharm.2007.12.030