| Augmentation of therapeutic efficacy in drug-resistant tumor models using ceramide coadministration in temporal-controlled polymer-blend nanoparticle delivery systems. | |
| | |
MedLine Citation:
|
PMID: 20143195 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
The development of multidrug resistance (MDR) is a major hindrance to cancer eradication as it renders tumors unresponsive to most chemotherapeutic treatments and is associated with cancer resurgence. This study describes a novel mechanism to overcome MDR through a polymer-blend nanoparticle platform that delivers a combination therapy of C6-ceramide (CER), a synthetic analog of an endogenously occurring apoptotic modulator, together with the chemotherapeutic drug paclitaxel (PTX), in a single formulation. The PTX/CER combination therapy circumvents another cellular mechanism whereby MDR develops, by lowering the threshold for apoptotic signaling. In vivo studies in a resistant subcutaneous SKOV3 human ovarian and in an orthotopic MCF7 human breast adenocarcinoma xenograft showed that the PTX and CER nanoparticle combination therapy reduced the final tumor volume at least twofold over treatment with the standard PTX therapy alone. The study also revealed that the cotherapy accomplished this enhanced efficacy by generating an enhancement in apoptotic signaling in both tumor types. Additionally, acute evaluation of safety with the combination therapy did not show significant changes in body weight, white blood cell counts, or liver enzyme levels. The temporal-controlled nanoparticle delivery system presented in this study allows for a simultaneous delivery of PTX + CER in breast and ovarian tumor model drug, leading to a modulation of the apoptotic threshold. This strategy has tremendous potential for effective treatment of refractory disease in cancer patients. |
| | |
Authors:
|
Lilian E van Vlerken; Zhenfeng Duan; Steven R Little; Michael V Seiden; Mansoor M Amiji |
Related Documents
:
|
1339155 - O6-methylguanine-dna methyltransferase activity and sensitivity of human tumor cell lin... 1618005 - Effect of a membrane-active agent on uptake of adriamycin in lewis lung carcinoma cells... 20528455 - Nanomedicinal strategies to treat multidrug-resistant tumors: current progress. 11142695 - The ex vivo effect of high concentrations of doxorubicin on recurrent ovarian carcinoma. 10714235 - Gnrh receptor and apoptotic signaling. 19929175 - Lines of cell differentiation in solitary fibrous tumor: an ultrastructural and immunoh... |
Publication Detail:
|
Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S. Date: 2010-02-09 |
Journal Detail:
|
Title: The AAPS journal Volume: 12 ISSN: 1550-7416 ISO Abbreviation: AAPS J Publication Date: 2010 Jun |
Date Detail:
|
Created Date: 2010-03-24 Completed Date: 2010-06-15 Revised Date: 2011-07-25 |
Medline Journal Info:
|
Nlm Unique ID: 101223209 Medline TA: AAPS J Country: United States |
Other Details:
|
Languages: eng Pagination: 171-80 Citation Subset: IM |
Affiliation:
|
Department of Pharmaceutical Sciences, School of Pharmacy, Northeastern University, Boston, Massachusetts 02115, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Animals Antineoplastic Agents / administration & dosage Antineoplastic Agents, Phytogenic / administration & dosage Antineoplastic Combined Chemotherapy Protocols / administration & dosage, adverse effects, therapeutic use* Body Weight / drug effects Cell Line, Tumor Ceramides / administration & dosage Chemistry, Pharmaceutical Drug Delivery Systems Drug Resistance, Multiple Drug Resistance, Neoplasm* Female Humans In Situ Nick-End Labeling Leukocyte Count Liver / enzymology Mice Mice, Nude Nanoparticles P-Glycoprotein / genetics Paclitaxel / administration & dosage Polymers Solubility |
| Grant Support | |
ID/Acronym/Agency:
|
R01-CA119617/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
|
0/ABCB1 protein, human; 0/Antineoplastic Agents; 0/Antineoplastic Agents, Phytogenic; 0/Ceramides; 0/P-Glycoprotein; 0/Polymers; 33069-62-4/Paclitaxel |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Biomaterials/tissue interactions: possible solutions to overcome foreign body response.
Next Document: Liposomal simvastatin attenuates neointimal hyperplasia in rats.