Document Detail


The microclimate pH in poly(D,L-lactide-co-hydroxymethyl glycolide) microspheres during biodegradation.
MedLine Citation:
PMID:  22819499     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The microclimate pH (μpH) in biodegradable polymers, such as poly(D,L-lactic-co-glycolic acid) (PLGA) 50/50, commonly falls to deleterious acidic levels during biodegradation, resulting in instability of encapsulated acid-labile molecules. The μpH distribution in microspheres of a more hydrophilic polyester, poly(D,L-lactide-co-hydroxymethyl glycolide) (PLHMGA), was measured and compared to that in PLGA 50/50 of similar molecular weight and degradation time scales. pH mapping in the polymers was performed after incubation under physiological conditions by using a previously validated ratiometric method employing confocal laser scanning microscopy (CLSM). Confocal μpH maps revealed that PLHMGA microspheres, regardless of copolymer composition, developed a far less acidic μpH during 4 weeks of incubation compared with microspheres from PLGA. A pH-independent fluorescent probe marker of polymer matrix diffusion of μpH-controlling water-soluble acid degradation products, bodipy, was observed by CLSM to diffuse ~3-7 fold more rapidly in PLHMGA compared to PLGA microspheres, consistent with much more rapid release of acids observed from the hydrophilic polymer during bioerosion. Hence, PLHMGA microspheres are less susceptible to acidification during degradation as compared to similar PLGA formulations, and therefore, PLHMGA may be more suitable to deliver acid labile molecules such as proteins.
Authors:
Yajun Liu; Amir H Ghassemi; Wim E Hennink; Steven P Schwendeman
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-07-21
Journal Detail:
Title:  Biomaterials     Volume:  33     ISSN:  1878-5905     ISO Abbreviation:  Biomaterials     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-08-13     Completed Date:  2012-12-18     Revised Date:  2013-11-15    
Medline Journal Info:
Nlm Unique ID:  8100316     Medline TA:  Biomaterials     Country:  England    
Other Details:
Languages:  eng     Pagination:  7584-93     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Elsevier Ltd. All rights reserved.
Affiliation:
Department of Pharmaceutical Science, University of Michigan, Ann Arbor, MI 48109, USA.
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MeSH Terms
Descriptor/Qualifier:
Acids / chemistry
Biodegradation, Environmental
Boron Compounds / chemistry
Chemistry, Pharmaceutical
Diffusion
Hydrogen-Ion Concentration
Kinetics
Lactic Acid / chemistry*
Microscopy, Confocal
Microscopy, Electron, Scanning
Microspheres*
Polyesters / chemistry*
Polyglycolic Acid / chemistry*
Solubility
Solutions
Water / chemistry
Grant Support
ID/Acronym/Agency:
R01 HL 68345/HL/NHLBI NIH HHS; R01 HL068345/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/4,4-difluoro-4-bora-3a,4a-diaza-s-indacene; 0/Acids; 0/Boron Compounds; 0/Polyesters; 0/Solutions; 0/poly(lactide-co-hydroxymethyl glycolide); 0/polylactic acid-polyglycolic acid copolymer; 26009-03-0/Polyglycolic Acid; 50-21-5/Lactic Acid; 7732-18-5/Water
Comments/Corrections

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