Interactions of Microbicide Nanoparticles with a Simulated Vaginal Fluid

• Type: Article in International Scientific Journal
• Date: 2012

Authors

José das Neves (Author) Other; Cristina Rocha (Author) FEUP; Maria Pilar Gonçalves (Author) FEUP; Rebecca L. Carrier (Author) Other; Mansoor Amiji (Author) Other; Maria Fernanda Bahia (Author) Other; Bruno Sarmento (Author) Other

Journal

Title: Molecular Pharmaceutics

Vol. 9

Pages: 3347-3356

ISSN: 1543-8384

Publisher: American Chemical Society

Indexing

ISI Web of Knowledge - 41 Citations

ISI Web of Science

Scopus - 51 Citations

Scientific classification

FOS: Engineering and technology > Other engineering and technologies

Other information

Authenticus ID: P-002-3H6

DOI: 10.1021/mp300408m

Abstract (EN): 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 (cetyltrimethylammonium bromide) surface charge. Studies were performed using the mucin particle method, rheological measurements, and real-time multiple particle tracking. Results showed that SVF presented rheological properties similar 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-fold, respectively. The estimated times required to cross a layer of SVF were equal to or lower than 1.7 h for negatively charged NPs, while for positively charged NPs these values were equal to or higher than 7 h. 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 interactions of nanosystems with mucus fluids or surrogates when considering mucosal drug delivery.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 10