Journal of Nanoparticle Research

, Volume 13, Issue 6, pp 2609–2623

Liposome-encapsulated EF24-HPβCD inclusion complex: a preformulation study and biodistribution in a rat model

  • H. Agashe
  • P. Lagisetty
  • K. Sahoo
  • D. Bourne
  • B. Grady
  • V. Awasthi
Research Paper

DOI: 10.1007/s11051-010-0154-5

Cite this article as:
Agashe, H., Lagisetty, P., Sahoo, K. et al. J Nanopart Res (2011) 13: 2609. doi:10.1007/s11051-010-0154-5

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 k1:1 value of 9.9 M−1. 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-t1/2 of 21.4 min and β-t1/2 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.

Keywords

CurcuminHydroxypropyl-β-cyclodextrinLiposomesEF24Inclusion complexNanomedicine

Copyright information

© Springer Science+Business Media B.V. 2010

Authors and Affiliations

  • H. Agashe
    • 1
  • P. Lagisetty
    • 1
  • K. Sahoo
    • 1
  • D. Bourne
    • 1
  • B. Grady
    • 2
  • V. Awasthi
    • 1
  1. 1.Department of Pharmaceutical SciencesUniversity of Oklahoma Health Sciences CenterOklahoma CityUSA
  2. 2.School of Chemical, Biological and Materials EngineeringNormanUSA