Document Detail


Inhibition of the transport of HIV in vitro using a pH-responsive synthetic mucin-like polymer system.
MedLine Citation:
PMID:  21875751     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
In conjunction with the routine role of delivering the active ingredient, carefully designed drug delivery vehicles can also provide ancillary functions that augment the overall efficacy of the system. Inspired by the ability of the cervicovaginal mucus to impede the movement of HIV virions at acidic pH, we have engineered a pH-responsive synthetic polymer that shows improved barrier properties over the naturally occurring cervicovaginal mucus by inhibiting viral transport at both acidic and neutral pH. The pH-responsive synthetic mucin-like polymer is constructed with phenylboronic acid (PBA) and salicylhydroxamic acid (SHA), each individually copolymerized with a 2-hydroxypropyl methacrylamide (pHPMA) polymer backbone. At pH 4.8, the crosslinked polymers form a transient network with a characteristic relaxation time of 0.9 s and elastic modulus of 11 Pa. On addition of semen, the polymers form a densely crosslinked elastic network with a characteristic relaxation time greater than 60 s and elastic modulus of 1800 Pa. Interactions between the PBA-SHA crosslinked polymers and mucin at acidic pH showed a significant increase in elastic modulus and crosslink lifetime (p < 0.05). A transport assay revealed that migration of HIV and cells was significantly impeded by the polymer network at pH ≥ 4.8 with a diffusion coefficient of 1.60 x 10(-4) μm(2)/s for HIV. Additionally, these crosslinked polymers did not induce symptoms of toxicity or irritation in either human vaginal explants or a mouse model. In summary, the pH-responsive crosslinked polymer system reported here holds promise as a class of microbicide delivery vehicle that could inhibit the transport of virions from semen to the target tissue and, thereby, contribute to the overall activity of the microbicide formulation.
Authors:
Alamelu Mahalingam; Julie I Jay; Kristofer Langheinrich; Shetha Shukair; Mike D McRaven; Lisa C Rohan; Betsy C Herold; Thomas J Hope; Patrick F Kiser
Publication Detail:
Type:  In Vitro; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-08-27
Journal Detail:
Title:  Biomaterials     Volume:  32     ISSN:  1878-5905     ISO Abbreviation:  Biomaterials     Publication Date:  2011 Nov 
Date Detail:
Created Date:  2011-09-19     Completed Date:  2012-01-20     Revised Date:  2014-09-22    
Medline Journal Info:
Nlm Unique ID:  8100316     Medline TA:  Biomaterials     Country:  England    
Other Details:
Languages:  eng     Pagination:  8343-55     Citation Subset:  IM    
Copyright Information:
Copyright © 2011 Elsevier Ltd. All rights reserved.
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MeSH Terms
Descriptor/Qualifier:
Animals
Boronic Acids / chemistry
Female
Fluorescent Dyes
HIV / drug effects*,  physiology
Humans
Hydrogen-Ion Concentration*
Macrophages / drug effects
Mice
Mucins / chemistry*
Polymers / chemistry,  pharmacology*
Rheology
Salicylamides / chemistry
Vagina / cytology,  drug effects
Grant Support
ID/Acronym/Agency:
R21 AI062445-01/AI/NIAID NIH HHS; R21 AI062445-02/AI/NIAID NIH HHS; R21-AI062445/AI/NIAID NIH HHS; R33 AI076968/AI/NIAID NIH HHS; R33 AI076968-03/AI/NIAID NIH HHS; R33 AI076968-04/AI/NIAID NIH HHS; R33 AI076968-05/AI/NIAID NIH HHS; R33-AI076968/AI/NIAID NIH HHS; T32-AI060523/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/Boronic Acids; 0/Fluorescent Dyes; 0/Mucins; 0/Polymers; 0/Salicylamides; 8Q07182D0T/salicylhydroxamic acid; L12H7B02G5/benzeneboronic acid
Comments/Corrections

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