| Rapid endo-lysosomal escape of poly(DL-lactide-co-glycolide) nanoparticles: implications for drug and gene delivery. | |
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MedLine Citation:
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PMID: 12153989 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The endo-lysosomal escape of drug carriers is crucial to enhancing the efficacy of their macromolecular payload, especially the payloads that are susceptible to lysosomal degradation. Current vectors that enable the endo-lysosomal escape of macromolecules such as DNA are limited by their toxicity and by their ability to carry only limited classes of therapeutic agents. In this paper, we report the rapid (<10 min) endo-lysosomal escape of biodegradable nanoparticles (NPs) formulated from the copolymers of poly(DL-lactide-co-glycolide) (PLGA). The mechanism of rapid escape is by selective reversal of the surface charge of NPs (from anionic to cationic) in the acidic endo-lysosomal compartment, which causes the NPs to interact with the endo-lysosomal membrane and escape into the cytosol. PLGA NPs are able to deliver a variety of therapeutic agents, including macromolecules such as DNA and low molecular weight drugs such as dexamethasone, intracellularly at a slow rate, which results in a sustained therapeutic effect. PLGA has a number of advantages over other polymers used in drug and gene delivery including biodegradability, biocompatibility, and approval for human use granted by the U.S. Food and Drug Administration. Hence PLGA is well suited for sustained intracellular delivery of macromolecules. |
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Authors:
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Jayanth Panyam; Wen-Zhong Zhou; Swayam Prabha; Sanjeeb K Sahoo; Vinod Labhasetwar |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: FASEB journal : official publication of the Federation of American Societies for Experimental Biology Volume: 16 ISSN: 1530-6860 ISO Abbreviation: FASEB J. Publication Date: 2002 Aug |
Date Detail:
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Created Date: 2002-08-02 Completed Date: 2002-09-03 Revised Date: 2012-02-15 |
Medline Journal Info:
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Nlm Unique ID: 8804484 Medline TA: FASEB J Country: United States |
Other Details:
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Languages: eng Pagination: 1217-26 Citation Subset: IM |
Affiliation:
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Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, Nebraska 68198, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Biological Transport Cell Division / drug effects Cell Line Cells, Cultured Delayed-Action Preparations Dexamethasone / administration & dosage, pharmacology Drug Carriers Endocytosis Endosomes / metabolism* Gene Therapy Growth Inhibitors / administration & dosage, pharmacology Humans Kinetics Lactic Acid / chemistry, metabolism* Lysosomes / metabolism* Male Models, Biological Muscle, Smooth, Vascular / cytology, drug effects Nanotechnology Particle Size Polyglycolic Acid / chemistry, metabolism* Polymers / chemistry, metabolism* Prostatic Neoplasms / metabolism Transfection |
| Grant Support | |
ID/Acronym/Agency:
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HL 57234/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Delayed-Action Preparations; 0/Drug Carriers; 0/Growth Inhibitors; 0/Polymers; 0/polylactic acid-polyglycolic acid copolymer; 26009-03-0/Polyglycolic Acid; 50-02-2/Dexamethasone; 50-21-5/Lactic Acid |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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