Document Detail


Surface modification of poly(lactic acid) nanoparticles by covalent attachment of thiol groups by means of three methods.
MedLine Citation:
PMID:  12527160     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The aim of the present work was to find a suitable method for the introduction of thiol functions on the surface of poly(DL-lactic acid) (PLA) nanoparticles. Three different approaches were investigated. The modification of the surface involves the activation of PLA carboxylic acid groups followed by the attack of a nucleophile such as cysteine (method #1) or cystamine (method #2 and #3) that provide thiol functions via an amide bond. For the conjugation with cystamine, a second reaction step is required to expose the sulfhydryl function of cystamine that is otherwise protected in a disulfide bond. 1,4-Dithio-DL-threitol (DTT) (method #2) or Tris(2-carboxyethyl)-phosphine hydrochloride (method #3) were evaluated for their ability to reduce this linkage. Method #1 allowed a maximum of 8.5+/-2.8 mmol of thiol functions per mol of PLA to be attached on the surface of the nanoparticles. Method #2 allowed the introduction of a greater number of thiol functions (up to 190+/-15 mmol per mol of PLA). However, this latter method has a major drawback: DTT interacts strongly with the nanoparticle matrix during the reduction step. Method #3 has the advantage over method #2 in that it allowed a significant number of thiol functions to be covalently bound to the particles (up to 107.6+/-0.6 mmol per mol of PLA) without the problem of undesired interaction between DTT and the nanoparticle matrix. The introduction of thiol groups onto the surface of PLA nanoparticles is possible with all three suggested methods. The method #3 provides a straight forward approach for the substitution of carboxylic acid groups with a high number of activated sulfhydryl at the surface of PLA nanoparticles.
Authors:
Leila Nobs; Franz Buchegger; Robert Gurny; Eric Allémann
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  International journal of pharmaceutics     Volume:  250     ISSN:  0378-5173     ISO Abbreviation:  Int J Pharm     Publication Date:  2003 Jan 
Date Detail:
Created Date:  2003-01-15     Completed Date:  2003-07-24     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  7804127     Medline TA:  Int J Pharm     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  327-37     Citation Subset:  IM    
Affiliation:
School of Pharmacy, University of Geneva, Quai Ernest-Ansermet 30, 1211 4, Geneva, Switzerland.
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MeSH Terms
Descriptor/Qualifier:
Lactic Acid / chemistry*
Nanotechnology / methods*
Polymers / chemistry*
Sulfhydryl Compounds / chemistry*
Surface Properties / drug effects
Technology, Pharmaceutical / methods*
Chemical
Reg. No./Substance:
0/Polymers; 0/Sulfhydryl Compounds; 26100-51-6/poly(lactic acid); 50-21-5/Lactic Acid

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


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