Document Detail


Development of a novel method for the preparation of thiolated polyacrylic acid nanoparticles.
MedLine Citation:
PMID:  16952008     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
PURPOSE: To develop a novel method for the preparation of thiolated polyacrylic acid nanoparticles via ionic gelation. MATERIALS AND METHODS: In a first step nanoparticles were generated by ionotropic gelation of polyacrylic acid (PAA) of three different molecular weights (100, 240 and 450 kDa) and various cations including Ca2+, Mg2+, Zn2+, Al3+ and Fe3+. Via in vitro characterization of the particles (particle size, size distribution and zeta potential) the optimal preparation conditions were established. Taking into consideration, that thiolated polyacrylic acid (PAA-Cys) displays higher mucoadhesive and permeation enhancing properties than unmodified PAA, PAA-Cys nanoparticles were produced in the same manner with Ca2+, as the most promising results concerning particle size and stability of particles could be achieved with this ionic crosslinker. The nanoparticles were stabilized via the formation of inter- and intrachain disulfide bonds within these particles due to oxidation with H2O2. Ca2+ was removed proximately by the addition of EDTA and exhaustive dialysis. RESULTS: Using the preparation method described above PAA-Cys nanoparticles of a mean diameter of about 220 nm (PAA(100)-Cys), 250 nm (PAA(240)-Cys) and 295 nm (PAA(450)-Cys) can be generated. In comparison to PAA nanoparticles ionically crosslinked with Ca2+, the removal of the crosslinker Ca2+ from PAA-Cys particles led to a nearly three-fold decrease in the zeta potential, from about -7 up to -20 mV. Apart from this advantage, covalently crosslinked PAA-Cys nanoparticles were more firm as they remained stable when incubated in hydrochloride solution, whereas ionically crosslinked particles dissolved at pH lower than 5. CONCLUSIONS: This novel nanoparticulate delivery system seems to be a promising vehicle for the administration of therapeutic proteins, genes and antigens via mucosal membranes.
Authors:
Melanie Greindl; Andreas Bernkop-Schnürch
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2006-08-09
Journal Detail:
Title:  Pharmaceutical research     Volume:  23     ISSN:  0724-8741     ISO Abbreviation:  Pharm. Res.     Publication Date:  2006 Sep 
Date Detail:
Created Date:  2006-09-04     Completed Date:  2006-10-30     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8406521     Medline TA:  Pharm Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2183-9     Citation Subset:  IM    
Affiliation:
Department of Pharmaceutical Technology, Institute of Pharmacy, Leopold-Franzens-University Innsbruck, Innrain 52, Josef-Möller-Haus, 6020 Innsbruck, Austria.
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MeSH Terms
Descriptor/Qualifier:
Acrylic Resins / chemistry*
Cations / chemistry
Cross-Linking Reagents
Disulfides / chemistry
Electrochemistry
Hydrogen Peroxide / chemistry
Hydrogen-Ion Concentration
Microscopy, Electron, Transmission
Molecular Weight
Nanostructures / chemistry*
Oxidants / chemistry
Particle Size
Sulfhydryl Compounds / chemistry*
Chemical
Reg. No./Substance:
0/Acrylic Resins; 0/Cations; 0/Cross-Linking Reagents; 0/Disulfides; 0/Oxidants; 0/Sulfhydryl Compounds; 7722-84-1/Hydrogen Peroxide; 9003-01-4/carbopol 940

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