Document Detail

Interactions of Microbicide Nanoparticles with a Simulated Vaginal Fluid.
MedLine Citation:
PMID:  23003680     Owner:  NLM     Status:  Publisher    
The interaction with cervicovaginal mucus presents the potential to impact the performance of drug nanocarriers. These systems must migrate through this biological fluid in order to deliver their drug payload to the underlying mucosal surface. We studied the ability of dapivirine-loaded polycaprolactone (PCL)-based nanoparticles (NPs) to interact with a simulated vaginal fluid (SVF) incorporating mucin. Different surface modifiers were used to produce NPs with either negative (poloxamer 338 NF and sodium lauryl sulfate) or positive (cetyl trimethylammonium bromide) surface charge. Studies were performed using the mucin particle method, rheological measurements and real-time multiple particle tracking. Results showed that SVF presented similar rheological properties to those of human cervicovaginal mucus. Analysis of NP transport indicated mild interactions with mucin and low adhesive potential. In general, negatively-charged NPs underwent subdiffusive transport in SVF, i.e. hindered as compared to their diffusion in water, but faster than for positively-charged NPs. These differences were increased when the pH of SVF was changed from 4.2 to 7.0. Diffusivity was 50- and 172-fold lower in SVF at pH 4.2 than in water for negatively-charged and positively-charged NPs, respectively. At pH 7.0, this decrease was around 20- and 385-folds, respectively. The estimated times required to cross a layer of SVF were equal to or lower than 1.7 hours for negatively-charged NPs, while for positively-charged NPs these values were equal to or higher than 7 hours. Overall, our results suggest that negatively-charged PCL NPs may be suitable to be used as carriers in order to deliver dapivirine and potentially other antiretroviral drugs to the cervicovaginal mucosal lining. Also, they further reinforce the importance in characterizing the interaction of nanosystems with mucus fluids or surrogates when considering mucosal drug delivery.
José das Neves; Cristina M R Rocha; Maria Pilar Goncalves; Rebecca L Carrier; Mansoor Amiji; Maria Fernanda Bahia; Bruno Sarmento
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-9-24
Journal Detail:
Title:  Molecular pharmaceutics     Volume:  -     ISSN:  1543-8392     ISO Abbreviation:  Mol. Pharm.     Publication Date:  2012 Sep 
Date Detail:
Created Date:  2012-9-25     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101197791     Medline TA:  Mol Pharm     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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