Document Detail


In vitro and in vivo evaluation of methoxy polyethylene glycol-polylactide (MPEG-PLA) nanoparticles for small-molecule drug chemotherapy.
MedLine Citation:
PMID:  17576004     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Methoxy polyethylene glycol-polylactide (MPEG-PLA) nanoparticles (NPs) were prepared by the nanoprecipitation method with particle size of 140+/-21nm in diameter and drug encapsulation efficiency of 87.6+/-3.1%. In vitro cytotoxicity of the drug formulated in the NPs was investigated with MCF-7 cancer cells in close comparison with that of Taxol((R)). The in vitro cytotoxicity with MCF-7 cells showed that the NP formulation could be 33.3, 10.7, 7.7 times more effective than Taxol((R)) after 24, 48, 72h culture at the same drug concentration of 1microg/ml. Confocal laser scanning microscopy (CLSM) visualized cellular internalization of the coumarin 6-loaded MPEG-PLA NPs. The in vitro results were further confirmed by the in vivo pharmacokinetic analysis with SD rats. The total area-under-the-curve (AUC(0-infinity)), which determines the therapeutic effects of a dose, was found to be 29,600+/-1,690ng-h/ml for the NP formulation, which is 3.09 times of 9,570+/-1,480ng-h/l for Taxol((R)) with 10mg/kg dose i.v. injection. The half-life (t(1/2)) of the drug formulated in the NPs was found to be 18.80+/-3.14h, which is 2.75 times of 6.84+/-1.39h for Taxol((R)). The distribution volume at steady state for the drug loaded in the NPs was 7.21+/-2.17l/kg, which was 2.93 times of 2.46+/-1.41l/kg for Taxol((R)). Our proof-of-concept in vitro and in vivo valuation shows that our MPEG-PLA NP formulation could have great advantages versus the original drug in small-molecule drug chemotherapy as well as in various applications in nanomedicine.
Authors:
Yuancai Dong; Si-Shen Feng
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Publication Detail:
Type:  Evaluation Studies; Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-06-18
Journal Detail:
Title:  Biomaterials     Volume:  28     ISSN:  0142-9612     ISO Abbreviation:  Biomaterials     Publication Date:  2007 Oct 
Date Detail:
Created Date:  2007-07-19     Completed Date:  2007-10-15     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8100316     Medline TA:  Biomaterials     Country:  England    
Other Details:
Languages:  eng     Pagination:  4154-60     Citation Subset:  IM    
Affiliation:
Department of Chemical and Biomolecular Engineering, National University of Singapore, Block E5, 02-11, 4 Engineering Drive 4, Singapore 117576, Singapore.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antineoplastic Agents, Phytogenic / chemistry,  metabolism,  therapeutic use
Cell Line, Tumor
Cell Survival
Drug Carriers / chemistry,  metabolism*
Drug Delivery Systems*
Humans
Male
Materials Testing
Nanoparticles / chemistry*
Neoplasms / drug therapy
Paclitaxel / chemistry,  metabolism,  therapeutic use
Particle Size
Polyesters / chemistry,  metabolism*
Polyethylene Glycols / chemistry,  metabolism*
Rats
Rats, Sprague-Dawley
Chemical
Reg. No./Substance:
0/Antineoplastic Agents, Phytogenic; 0/Drug Carriers; 0/Polyesters; 0/Polyethylene Glycols; 26969-66-4/poly(lactide); 33069-62-4/Paclitaxel

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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