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- Title
Liposome-encapsulated EF24-HPβCD inclusion complex: a preformulation study and biodistribution in a rat model.
- Authors
Agashe, H.; Lagisetty, P.; Sahoo, K.; Bourne, D.; Grady, B.; Awasthi, V.
- Abstract
3,5-Bis(2-fluorobenzylidene)-4-piperidone (EF24) is an anti-proliferative diphenyldifluoroketone analog of curcumin with more potent activity. The authors describe a liposome preparation of EF24 using a 'drug-in-CD-in liposome' approach. An aqueous solution of EF24 and hydroxypropyl-β-cyclodextrin (HPβCD) inclusion complex (IC) was used to prepare EF24 liposomes. The liposome size was reduced by a combination of multiple freeze-thaw cycles. Co-encapsulation of glutathione inside the liposomes conferred them with the capability of labeling with imageable radionuclide Tc-99m. Phase solubility analysis of EF24-HPβCD mixture provided k value of 9.9 M. The enhanced aqueous solubility of EF24 (from 1.64 to 13.8 mg/mL) due to the presence of HPβCD helped in the liposome preparation. About 19% of the EF24 IC was encapsulated inside the liposomes (320.5 ± 2.6 nm) by dehydration-rehydration technique. With extrusion technique, the size of 177 ± 6.5 nm was obtained without any effect on encapsulation efficiency. The EF24-liposomes were evaluated for anti-proliferative activity in lung adenocarcinoma H441 and prostate cancer PC-3 cells. The EF24-liposomes demonstrated anti-proliferative activity superior to that of plain EF24 at 10 μM dose. When injected in rats, the Tc-99m-labeled EF24-liposomes cleared from blood with an α- t of 21.4 min and β- t of 397 min. Tissue radioactivity counting upon necropsy showed that the majority of clearance was due to the uptake in liver and spleen. The results suggest that using 'drug-in-CD-in liposome' approach is a feasible strategy to formulate an effective parenteral preparation of EF24. In vitro studies show that the liposomal EF24 remains anti-proliferative, while presenting an opportunity to image its biodistribution.
- Subjects
LIPOSOMES; NANOMEDICINE; MICROENCAPSULATION; PHENOLS; LABORATORY rats; PIPERIDONES; CYCLODEXTRINS; CANCER cell proliferation; THERAPEUTICS; PREVENTION
- Publication
Journal of Nanoparticle Research, 2011, Vol 13, Issue 6, p2609
- ISSN
1388-0764
- Publication type
Academic Journal
- DOI
10.1007/s11051-010-0154-5