| PEGylated J591 mAb loaded in PLGA-PEG-PLGA tri-block copolymer for targeted delivery: in vitro evaluation in human prostate cancer cells. | |
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MedLine Citation:
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PMID: 16713147 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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J591 monoclonal antibody (mAb) has high affinity for prostate specific membrane antigen (PSMA) on prostate cancer (PCA) cells. We coupled polyethylene glycol-J591 (PEGylated J591) to a salicyl hydroxamic acid (SHA)-derivatized polyethylenimine (PEI)/DNA-betagal vector to investigate the specificity and efficiency of targeting PSMA in PCA cells through encapsulation. Coupling was facilitated via the high affinity interaction between phenyl(di)boronic acid (PDBA) and SHA molecules yielding J591/PEG/PEI/DNA-betagal polyplex. After encapsulation with poly(d,l-lactic-co-glycolic acid)-b-polyethylene glycol-b-poly(d,l-lactic-co-glycolic acid) (PLGA-PEG-PLGA) tri-block copolymer, 8-10-fold increment of gene transfection levels were attained at the optimum concentration of 0.25% (w/v) using Pluronic F68 tri-block copolymer as a control. The enhanced transfection efficiency was attributed to increased internalization and uptake of the radiolabeled plasmid in the presence of PLGA-PEG-PLGA tri-block copolymer. The release of plasmid DNA (pDNA) from microparticles containing SHA-PEI-complexed pDNA showed little initial burst release followed by a 5% release over 48 h. The release accelerated thereafter and approximately 60% was released after 28 days. Deconvolution confocal microscopy showed polyplex/microparticle formulation localized in the cell nucleus as opposed to the polyplex without PLGA-PEG-PLGA indicating that an optimal concentration of PLGA-PEG-PLGA tri-block copolymer can be utilized to enhance endocytic process of J591-mediated targeting of PCA cells. |
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Authors:
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Stanley Moffatt; Richard J Cristiano |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2006-05-19 |
Journal Detail:
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Title: International journal of pharmaceutics Volume: 317 ISSN: 0378-5173 ISO Abbreviation: Int J Pharm Publication Date: 2006 Jul |
Date Detail:
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Created Date: 2006-06-19 Completed Date: 2006-12-12 Revised Date: 2011-08-01 |
Medline Journal Info:
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Nlm Unique ID: 7804127 Medline TA: Int J Pharm Country: Netherlands |
Other Details:
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Languages: eng Pagination: 10-3 Citation Subset: IM |
Affiliation:
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Laboratory of Experimental Therapeutics, Department of Genitourinary Medical Oncology, University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, 77030, USA. Stanley-moffatt@excite.com |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Antibodies, Monoclonal
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administration & dosage*,
chemistry Cell Line, Tumor DNA / administration & dosage Drug Delivery Systems* Humans Lactic Acid / chemistry Male Plasmids Polyethylene Glycols / chemistry Polyethyleneimine / chemistry Polyglycolic Acid / chemistry Polymers / chemistry Prostatic Neoplasms Transfection / methods |
| Grant Support | |
ID/Acronym/Agency:
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5P30-CA016672-29/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Antibodies, Monoclonal; 0/J591 monoclonal antibody; 0/Polyethylene Glycols; 0/Polymers; 0/polylactic acid-polyglycolic acid copolymer; 26009-03-0/Polyglycolic Acid; 50-21-5/Lactic Acid; 9002-98-6/Polyethyleneimine; 9007-49-2/DNA |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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