Document Detail

A novel class of photo-triggerable liposomes containing DPPC:DC(8,9)PC as vehicles for delivery of doxorubcin to cells.
MedLine Citation:
PMID:  20691151     Owner:  NLM     Status:  MEDLINE    
Success of nanoparticle-mediated drug delivery is subject to development of optimal drug release strategies within defined space and time (triggered release). Recently, we reported a novel class of photo-triggerable liposomes prepared from dipalmitoyl phosphatidylcholine (DPPC) and photopolymerizable diacetylene phospholipid (DC(8),(9)PC), that efficiently released entrapped calcein (a water soluble fluorescent dye) upon UV (254nm) treatment. To develop these formulations for in vivo applications, we have examined phototriggering of these liposomes by visible light, and the effect of released anticancer drugs on cellular toxicity. Sonicated liposomes containing various ratios of DPPC:DC(8),(9)PC and 4mol% DSPE-PEG2000 were loaded with calcein (Ex/Em, 485/517nm) or a chemotherapy drug, Doxorubicin (DOX, Ex/Em 490/590nm). Our initial experiments showed that 514nm laser treatment of liposomes containing 10 or 20mol% DC(8,9)PC for 1-3min resulted in significant release of calcein. Based on these results, we performed studies with DOX-loaded liposomes. First, biophysical properties (including liposome size and stability) and DOX encapsulation efficiency of the liposomes were determined. Subsequently, the effect of 514nm laser on DOX release, and cellular toxicity by released DOX were examined. Since liposomes using the 86:10:04 mole ratio of DPPC:DC(8),(9)PC:DSPE-PEG2000, showed highest encapsulation of DOX, these formulations were investigated further. We report that (i) liposomes retained about 70% of entrapped DOX at 37°C in the presence of 0-50% serum. (ii) 514nm laser treatment resulted in DOX release from liposomes in a wavelength-specific manner. (iii) Laser treatment of co-cultures containing DOX-loaded liposomes and cells (Raji and MCF-7) resulted in at least 2-3 fold improved cell killing as compared to untreated samples. Taken together, the photo-triggerable liposomes described here may provide a platform for future drug delivery applications. To our knowledge, this is the first report demonstrating improved cell killing following light-triggered release of an encapsulated anticancer agent from photosensitive liposomes.
Amichai Yavlovich; Alok Singh; Robert Blumenthal; Anu Puri
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2010-08-04
Journal Detail:
Title:  Biochimica et biophysica acta     Volume:  1808     ISSN:  0006-3002     ISO Abbreviation:  Biochim. Biophys. Acta     Publication Date:  2011 Jan 
Date Detail:
Created Date:  2010-12-06     Completed Date:  2011-03-07     Revised Date:  2013-05-29    
Medline Journal Info:
Nlm Unique ID:  0217513     Medline TA:  Biochim Biophys Acta     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  117-26     Citation Subset:  IM    
Copyright Information:
Published by Elsevier B.V.
Membrane Structure and Function Section, Nanobiology Program, NCI-Frederick, Frederick, MD 21702, USA.
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MeSH Terms
1,2-Dipalmitoylphosphatidylcholine / chemistry*
Antineoplastic Agents / administration & dosage
Biophysics / methods
Cell Line, Tumor
Coculture Techniques
Doxorubicin / administration & dosage*,  chemistry*
Drug Carriers
Drug Delivery Systems
Fluorescent Dyes / chemistry
Liposomes / chemistry*
Phosphatidylcholines / chemistry
Water / chemistry
Grant Support
Reg. No./Substance:
0/Antineoplastic Agents; 0/Drug Carriers; 0/Fluorescent Dyes; 0/Liposomes; 0/Phosphatidylcholines; 23214-92-8/Doxorubicin; 2644-64-6/1,2-Dipalmitoylphosphatidylcholine; 7732-18-5/Water

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