Document Detail

The intracellular drug delivery and anti tumor activity of doxorubicin loaded poly(gamma-benzyl L-glutamate)-b-hyaluronan polymersomes.
MedLine Citation:
PMID:  20053435     Owner:  NLM     Status:  MEDLINE    
We have investigated the intracellular delivery of doxorubicin (DOX) loaded poly(gamma-benzyl L-glutamate)-block-hyaluronan (PBLG-b-HYA) based polymersomes (PolyDOX) in high (MCF-7) and low (U87) CD44 expressing cancer cell models. DOX was successfully loaded into polymersomes using nanoprecipitation method and in vitro drug release pattern were achieved at pH 5.5 and 7.4 up to 10 days. Block copolymer vesicles without loaded DOX were non cytotoxic in both cells at concentration 150-650 microg/mL. Flow cytometry data suggested successful uptake of PolyDOX in cells and high accumulation was found in MCF-7 than U87 cells. Microscopy imagings revealed that in MCF-7 cells PolyDOX was more in cytoplasm and free DOX in nuclei, whereas in U87 cells free DOX was also found in the cytoplasm. Cytotoxicity of the drug was concentration and exposure time dependent. In addition, PolyDOX significantly enhanced reactive oxygen species (ROS) level in both cells. PolyDOX also suppressed growth of breast tumor on female Sprague-Dawley (SD) rats as compared to phosphate buffer saline pH 7.4 (PBS) control group. In addition reduced level of serum enzymes (LDH and CPK) by PolyDOX formulation indicated less cardiotoxicity of DOX after loading in polymersomes. Results suggest that intracellular delivery of PolyDOX was depended on the CD44 expression level in cells due to presence of hyaluronic acid on the surface of polymersomes, and could be used as a self-targeting drug delivery cargo in over-expressed CD44 glycoprotein cells of breast cancer.
Kamal K Upadhyay; Anant N Bhatt; Anil K Mishra; Bilikere S Dwarakanath; Sanyog Jain; Christophe Schatz; Jean-Fran?ois Le Meins; Abdullah Farooque; Godugu Chandraiah; Amit K Jain; Ambikanandan Misra; S?bastien Lecommandoux
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-01-06
Journal Detail:
Title:  Biomaterials     Volume:  31     ISSN:  1878-5905     ISO Abbreviation:  Biomaterials     Publication Date:  2010 Apr 
Date Detail:
Created Date:  2010-02-09     Completed Date:  2010-05-04     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8100316     Medline TA:  Biomaterials     Country:  England    
Other Details:
Languages:  eng     Pagination:  2882-92     Citation Subset:  IM    
Copyright Information:
2009 Elsevier Ltd. All rights reserved.
Universit? de Bordeaux, UMR5629, ENSCPB, 16, Avenue Pey Berland, 33607 Pessac-Cedex, France.
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MeSH Terms
Antigens, CD44 / metabolism
Antineoplastic Agents / pharmacology*
Cardiotoxins / pharmacology
Cell Death / drug effects
Cell Line, Tumor
Cell Survival / drug effects
Creatine Kinase / blood
Doxorubicin / administration & dosage,  pharmacology*
Drug Delivery Systems*
Flow Cytometry
Hyaluronic Acid / analogs & derivatives*,  pharmacology
Hydrogen-Ion Concentration / drug effects
Intracellular Space / drug effects,  metabolism*
Kaplan-Meiers Estimate
L-Lactate Dehydrogenase / blood
Microscopy, Electron, Transmission
Microscopy, Fluorescence
Polyglutamic Acid / analogs & derivatives*,  pharmacology
Rats, Sprague-Dawley
Reactive Oxygen Species / metabolism
Reg. No./Substance:
0/Antigens, CD44; 0/Antineoplastic Agents; 0/Cardiotoxins; 0/Reactive Oxygen Species; 0/poly(gamma-benzyl glutamate)-b-hyaluronan; 23214-92-8/Doxorubicin; 25014-27-1/poly-gamma-benzyl-L-glutamate; 25513-46-6/Polyglutamic Acid; 9004-61-9/Hyaluronic Acid; EC Dehydrogenase; EC Kinase

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