Document Detail


Lysosomal degradability of poly(alpha-amino acids).
MedLine Citation:
PMID:  9086408     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The lysosomal degradability of poly(alpha-amino acids) based on poly(L-glutamic acid) and its derivatives/copolymers was evaluated to gain insight into the subcellular fate of the macromolecules as water soluble polymeric drug carriers. The results indicate that both the incorporation of hydrophobic comonomers and modification of the carboxylic groups of glutamic acid side chains with hydroxyalkylamine increase the lysosomal degradability of the copolymers. Decreased lysosomal degradability of L-glutamic acid copolymers containing tripeptides terminated in p-nitroanilide (drug model) in the side chains confirmed that drug conjugation alters the degradation pattern of the polymeric carriers. The percentages of the enzymatic release of p-nitroaniline from its polymeric complex with time is relatively independent of the contents of the tripeptidyl p-nitroanilides attached to the polymeric conjugates. Determination of the degradation products by electrospray mass spectroscopy showed that no fragments less than 10(3) D were generated by lysosomal enzymes, whereas the main degradation products by papain and chymotrypsin were tripeptides and tetrapeptides. The conclusions derived from these data strongly suggest that these macromolecules, if used as lysosomotropic drug carriers, may accumulate in the lysosomes and limit their usefulness in some applications.
Authors:
H C Chiu; P Kopecková; S S Deshmane; J Kopecek
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Publication Detail:
Type:  In Vitro; Journal Article    
Journal Detail:
Title:  Journal of biomedical materials research     Volume:  34     ISSN:  0021-9304     ISO Abbreviation:  J. Biomed. Mater. Res.     Publication Date:  1997 Mar 
Date Detail:
Created Date:  1997-06-20     Completed Date:  1997-06-20     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0112726     Medline TA:  J Biomed Mater Res     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  381-92     Citation Subset:  IM    
Affiliation:
Department of Bioengineering, University of Utah, Salt Lake City, Utah 84112, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Biocompatible Materials / chemistry,  metabolism*
Drug Carriers / chemistry,  metabolism
Lysosomes / metabolism*
Mass Spectrometry
Materials Testing
Oligopeptides / chemistry,  metabolism
Peptides / chemistry,  metabolism*
Polyglutamic Acid / analogs & derivatives,  chemistry,  metabolism
Rats
Chemical
Reg. No./Substance:
0/Biocompatible Materials; 0/Drug Carriers; 0/Oligopeptides; 0/Peptides; 25513-46-6/Polyglutamic Acid

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


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