



@article {3275,
	title = {Biodistribution and pharmacokinetics of Dapivirine-loaded nanoparticles after vaginal delivery in mice},
	journal = {Pharmaceutical Research},
	volume = {31},
	year = {2014},
	note = {Cited By (since 1996):2Export Date: 21 November 2014},
	month = {2014},
	pages = {1834 - 1845},
	abstract = {Purpose: To assess the potential of polymeric nanoparticles (NPs) to affect the genital distribution and local and systemic pharmacokinetics (PK) of the anti-HIV microbicide drug candidate dapivirine after vaginal delivery. Methods: Dapivirine-loaded, poly(ethylene oxide)-coated poly(epsilon-caprolactone) (PEO-PCL) NPs were prepared by a nanoprecipitation method. Genital distribution of NPs and their ability to modify the PK of dapivirine up to 24 h was assessed after vaginal instillation in a female mouse model. Also, the safety of NPs upon daily administration for 14 days was assessed by histological analysis and chemokine/cytokine content in vaginal lavages. Results: PEO-PCL NPs (180-200 nm) were rapidly eliminated after administration but able to distribute throughout the vagina and lower uterus, and capable of tackling mucus and penetrate the epithelial lining. Nanocarriers modified the PK of dapivirine, with higher drug levels being recovered from vaginal lavages and vaginal/lower uterine tissues as compared to a drug suspension. Systemic drug exposure was reduced when NPs were used. Also, NPs were shown safe upon administration for 14 days. Conclusions: Dapivirine-loaded PEO-PCL NPs were able to provide likely favorable genital drug levels, thus attesting the potential value of using this vaginal drug delivery nanosystem in the context of HIV prophylaxis. {\textcopyright} 2014 Springer Science+Business Media New York.},
	keywords = {HIV/AIDS, microbicides, poly(ε-caprolactone), pre-exposure prophylaxis, vaginal drug delivery},
	url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84904252215\&partnerID=40\&md5=e50091fa44bc3ac794251baa9e57d736},
	author = {Das Neves, J. and Ara{\'u}jo, F. and Andrade, F. and Amiji, M. and Bahia, M.F. and Sarmento, B.}
}
@article {2846,
	title = {Assessing the physical-chemical properties and stability of dapivirine-loaded polymeric nanoparticles},
	journal = {International Journal of Pharmaceutics},
	volume = {456},
	year = {2013},
	note = {Export Date: 12 December 2013Source: Scopus},
	month = {2013///},
	pages = {307 - 314},
	url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84884308158\&partnerID=40\&md5=52f91c19cbe922064bbdc786298301a0},
	author = {Das Neves, J. and Amiji, M. and Bahia, M.F. and Sarmento, B.}
}
@article {2857,
	title = {In vitro and Ex Vivo evaluation of polymeric nanoparticles for vaginal and rectal delivery of the anti-HIV drug dapivirine},
	journal = {Molecular Pharmaceutics},
	volume = {10},
	year = {2013},
	note = {Cited By (since 1996):1Export Date: 12 December 2013Source: Scopus},
	month = {2013///},
	pages = {2793 - 2807},
	url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84879736868\&partnerID=40\&md5=cd7771212c94b7031331e338743b05ed},
	author = {Das Neves, J. and Ara{\'u}jo, F. and Andrade, F. and Michiels, J. and Ari{\"e}n, K.K. and Vanham, G. and Amiji, M. and Bahia, M.F. and Sarmento, B.}
}
@article {2181,
	title = {Interactions of microbicide nanoparticles with a simulated vaginal fluid},
	journal = {Molecular PharmaceuticsMol. Pharm.},
	volume = {9},
	year = {2012},
	note = {Export Date: 21 November 2012Source: ScopusCODEN: MPOHBdoi: 10.1021/mp300408mLanguage of Original Document: EnglishCorrespondence Address: Das Neves, J.; Laboratory of Pharmaceutical Technology, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal; email: j.dasneves@gmail.comReferences: Abdool Karim, Q., Abdool Karim, S.S., Frohlich, J.A., Grobler, A.C., Baxter, C., Mansoor, L.E., Kharsany, A.B., Taylor, D., Effectiveness and safety of tenofovir gel, an antiretroviral microbicide, for the prevention of HIV infection in women (2010) Science, 329, pp. 1168-1174;Ari{\"e}n, K.K., Jespers, V., Vanham, G., HIV sexual transmission and microbicides (2011) Rev. Med. Virol., 21, pp. 110-133; 
Rohan, L.C., Sassi, A.B., Vaginal drug delivery systems for HIV prevention (2009) AAPS J., 11, pp. 78-87; 
Das Neves, J., Amiji, M.M., Bahia, M.F., Sarmento, B., Nanotechnology-based systems for the treatment and prevention of HIV/AIDS (2010) Adv. Drug Delivery Rev., 62, pp. 458-477; 
Das Neves, J., Bahia, M.F., Amiji, M.M., Sarmento, B., Mucoadhesive nanomedicines: Characterization and modulation of mucoadhesion at the nanoscale (2011) Expert Opin. Drug Delivery, 8, pp. 1085-1104; 
Cone, R.A., Barrier properties of mucus (2009) Adv. Drug Delivery Rev., 61, pp. 75-85; 
Ensign, L.M., Cone, R., Hanes, J., Oral drug delivery with polymeric nanoparticles: The gastrointestinal mucus barriers (2012) Adv. Drug Delivery Rev., 64, pp. 557-570; 
Das Neves, J., Amiji, M., Sarmento, B., Mucoadhesive nanosystems for vaginal microbicide development: Friend or foe? (2011) Wiley Interdiscip. Rev.: Nanomed. Nanobiotechnol., 3, pp. 389-399; 
Suh, J., Wirtz, D., Hanes, J., Efficient active transport of gene nanocarriers to the cell nucleus (2003) Proc. Natl. Acad. Sci. U.S.A., 100, pp. 3878-3882; 
Suk, J.S., Lai, S.K., Wang, Y.Y., Ensign, L.M., Zeitlin, P.L., Boyle, M.P., Hanes, J., The penetration of fresh undiluted sputum expectorated by cystic fibrosis patients by non-adhesive polymer nanoparticles (2009) Biomaterials, 30, pp. 2591-2597; 
Crater, J.S., Carrier, R.L., Barrier properties of gastrointestinal mucus to nanoparticle transport (2010) Macromol. Biosci., 10 (12), pp. 1473-1483; 
Dawson, M., Krauland, E., Wirtz, D., Hanes, J., Transport of polymeric nanoparticle gene carriers in gastric mucus (2004) Biotechnol. Prog., 20, pp. 851-857; 
Lieleg, O., Vladescu, I., Ribbeck, K., Characterization of particle translocation through mucin hydrogels (2010) Biophys. J., 98, pp. 1782-1789; 
Lai, S.K., Ohanlon, D.E., Harrold, S., Man, S.T., Wang, Y.Y., Cone, R., Hanes, J., Rapid transport of large polymeric nanoparticles in fresh undiluted human mucus (2007) Proc. Natl. Acad. Sci. U.S.A., 104, pp. 1482-1487; 
Tang, B.C., Dawson, M., Lai, S.K., Wang, Y.Y., Suk, J.S., Yang, M., Zeitlin, P., Hanes, J., Biodegradable polymer nanoparticles that rapidly penetrate the human mucus barrier (2009) Proc. Natl. Acad. Sci. U.S.A., 106, pp. 19268-19273; 
Suh, J., Dawson, M., Hanes, J., Real-time multiple-particle tracking: Applications to drug and gene delivery (2005) Adv. Drug Delivery Rev., 57, pp. 63-78; 
Wang, Y.Y., Lai, S.K., Suk, J.S., Pace, A., Cone, R., Hanes, J., Addressing the PEG mucoadhesivity paradox to engineer nanoparticles that "slip" through the human mucus barrier (2008) Angew. Chem., Int. Ed., 47, pp. 9726-9729; 
Cu, Y., Saltzman, W.M., Controlled surface modification with poly(ethylene)glycol enhances diffusion of PLGA nanoparticles in human cervical mucus (2009) Mol. Pharmaceutics, 6, pp. 173-181; 
Yang, M., Lai, S.K., Wang, Y.Y., Zhong, W., Happe, C., Zhang, M., Fu, J., Hanes, J., Biodegradable nanoparticles composed entirely of safe materials that rapidly penetrate human mucus (2011) Angew. Chem., Int. Ed., 50, pp. 2597-2600; 
Ensign, L.M., Tang, B.C., Wang, Y.Y., Tse, T.A., Hoen, T., Cone, R., Hanes, J., Mucus-penetrating nanoparticles for vaginal drug delivery protect against herpes simplex virus (2012) Sci. Transl. Med., 4, pp. 138ra79; 
Alexis, F., Pridgen, E., Molnar, L.K., Farokhzad, O.C., Factors affecting the clearance and biodistribution of polymeric nanoparticles (2008) Mol. Pharmaceutics, 5, pp. 505-515; 
Zahr, A.S., Davis, C.A., Pishko, M.V., Macrophage uptake of core-shell nanoparticles surface modified with poly(ethylene glycol) (2006) Langmuir, 22, pp. 8178-8185; 
Das Neves, J., Michiels, J., Arien, K.K., Vanham, G., Amiji, M., Bahia, M.F., Sarmento, B., Polymeric nanoparticles affect the intracellular delivery, antiretroviral activity and cytotoxicity of the microbicide drug candidate dapivirine (2012) Pharm. Res., 29, pp. 1468-1484; 
Das Neves, J., Sarmento, B., Amiji, M.M., Bahia, M.F., Development and validation of a rapid reversed-phase HPLC method for the determination of the non-nucleoside reverse transcriptase inhibitor dapivirine from polymeric nanoparticles (2010) J. Pharm. Biomed. Anal., 52, pp. 167-172; 
Owen, D.H., Katz, D.F., A vaginal fluid simulant (1999) Contraception, 59, pp. 91-95; 
Lee, C.H., Wang, Y., Shin, S.C., Chien, Y.W., Effects of chelating agents on the rheological property of cervical mucus (2002) Contraception, 65, pp. 435-440; 
Vermani, K., Garg, S., Zaneveld, L.J., Assemblies for in vitro measurement of bioadhesive strength and retention characteristics in simulated vaginal environment (2002) Drug Dev. Ind. Pharm., 28, pp. 1133-1146; 
Das Neves, J., Amaral, M.H., Bahia, M.F., Performance of an in vitro mucoadhesion testing method for vaginal semisolids: Influence of different testing conditions and instrumental parameters (2008) Eur. J. Pharm. Biopharm., 69, pp. 622-632; 
Takeuchi, H., Thongborisute, J., Matsui, Y., Sugihara, H., Yamamoto, H., Kawashima, Y., Novel mucoadhesion tests for polymers and polymer-coated particles to design optimal mucoadhesive drug delivery systems (2005) Adv. Drug Delivery Rev., 57, pp. 1583-1594; 
Grenha, A., Chitosan nanoparticles: A survey of preparation methods (2012) J. Drug Targeting, 20, pp. 291-300; 
Bravo-Osuna, I., Vauthier, C., Farabollini, A., Palmieri, G.F., Ponchel, G., Mucoadhesion mechanism of chitosan and thiolated chitosan-poly(isobutyl cyanoacrylate) core-shell nanoparticles (2007) Biomaterials, 28, pp. 2233-2243; 
Sbalzarini, I.F., Koumoutsakos, P., Feature point tracking and trajectory analysis for video imaging in cell biology (2005) J. Struct. Biol., 151, pp. 182-195; 
Saxton, M.J., Jacobson, K., Single-particle tracking: Applications to membrane dynamics (1997) Annu. Rev. Biophys. Biomol. Struct., 26, pp. 373-399; 
Lai, S.K., Wang, Y.Y., Hanes, J., Mucus-penetrating nanoparticles for drug and gene delivery to mucosal tissues (2009) Adv. Drug Delivery Rev., 61, pp. 158-171; 
Boskey, E.R., Telsch, K.M., Whaley, K.J., Moench, T.R., Cone, R.A., Acid production by vaginal flora in vitro is consistent with the rate and extent of vaginal acidification (1999) Infect. Immun., 67, pp. 5170-5175; 
Mason, T.G., Ganesan, K., Van Zanten, J.H., Wirtz, D., Kuo, S.C., Particle tracking microrheology of complex fluids (1997) Phys. Rev. Lett., 79, pp. 3282-3285; 
Mason, T.G., Estimating the viscoelastic moduli of complex fluids using the generalized Stokes-Einstein equation (2000) Rheol. Acta, 39, pp. 371-378; 
Lai, S.K., Wang, Y.Y., Cone, R., Wirtz, D., Hanes, J., Altering mucus rheology to "solidify" human mucus at the nanoscale (2009) PLoS One, 4, p. 4294; 
Lai, S.K., Wang, Y.Y., Hida, K., Cone, R., Hanes, J., Nanoparticles reveal that human cervicovaginal mucus is riddled with pores larger than viruses (2010) Proc. Natl. Acad. Sci. U.S.A., 107, pp. 598-603; 
Shenoy, D.B., Amiji, M.M., Poly(ethylene oxide)-modified poly(epsilon-caprolactone) nanoparticles for targeted delivery of tamoxifen in breast cancer (2005) Int. J. Pharm., 293, pp. 261-270; 
Shah, L.K., Amiji, M.M., Intracellular delivery of saquinavir in biodegradable polymeric nanoparticles for HIV/AIDS (2006) Pharm. Res., 23, pp. 2638-2645; 
McGill, S., Smyth, H., Disruption of the mucus barrier by topically applied exogenous particles (2010) Mol. Pharmaceutics, 7, pp. 2280-2288; 
Das Neves, J., Amaral, M.H., Bahia, M.F., Vaginal Drug Delivery (2008) Pharmaceutical Manufacturing Handbook: Production and Processes, pp. 809-878. , Gad, S. C. Wiley: Hoboken, NJ; 
Lai, S.K., Hida, K., Shukair, S., Wang, Y.Y., Figueiredo, A., Cone, R., Hope, T.J., Hanes, J., Human immunodeficiency virus type 1 is trapped by acidic but not by neutralized human cervicovaginal mucus (2009) J. Virol., 83, pp. 11196-11200; 
Cone, R.A., Mucus (2005) Mucosal Immunology, pp. 49-72. , In, 3 rd ed. Mestecky, J. Lamm, M. E. Strober, W. Bienenstock, J. McGhee, J. R. Mayer, L. Academic Press: San Diego, CA; 
Katz, D.F., Human cervical mucus: Research update (1991) Am. J. Obstet. Gynecol., 165, pp. 1984-1986; 
Das Neves, J., Da Silva, M.V., Gon{\c c}alves, M.P., Amaral, M.H., Bahia, M.F., Rheological properties of vaginal hydrophilic polymer gels (2009) Curr. Drug Delivery, 6, pp. 83-92; 
Celli, J.P., Turner, B.S., Afdhal, N.H., Ewoldt, R.H., McKinley, G.H., Bansil, R., Erramilli, S., Rheology of gastric mucin exhibits a pH-dependent sol-gel transition (2007) Biomacromolecules, 8, pp. 1580-1586; 
Madsen, F., Eberth, K., Smart, J.D., A rheological examination of the mucoadhesive/mucus interaction: The effect of mucoadhesive type and concentration (1998) J. Controlled Release, 50, pp. 167-178; 
Koc{\ae}evar-Nared, J., Kristl, J., S{\ae}mid-Korbar, J., Comparative rheological investigation of crude gastric mucin and natural gastric mucus (1997) Biomaterials, 18, pp. 677-681; 
Waigh, T.A., Papagiannopoulos, A., Voice, A., Bansil, R., Unwin, A.P., Dewhurst, C.D., Turner, B., Afdhal, N., Entanglement coupling in porcine stomach mucin (2002) Langmuir, 18, pp. 7188-7195; 
Rossi, S., Ferrari, F., Bonferoni, M.C., Caramella, C., Characterization of chitosan hydrochloride-mucin rheological interaction: Influence of polymer concentration and polymer:mucin weight ratio (2001) Eur. J. Pharm. Sci., 12, pp. 479-485; 
Sriamornsak, P., Wattanakorn, N., Rheological synergy in aqueous mixtures of pectin and mucin (2008) Carbohydr. Polym., 74, pp. 474-481; 
Shen, J., Wang, Y., Ping, Q., Xiao, Y., Huang, X., Mucoadhesive effect of thiolated PEG stearate and its modified NLC for ocular drug delivery (2009) J. Controlled Release, 137, pp. 217-223; 
Boukari, H., Brichacek, B., Stratton, P., Mahoney, S.F., Lifson, J.D., Margolis, L., Nossal, R., Movements of HIV-virions in human cervical mucus (2009) Biomacromolecules, 10, pp. 2482-2488; 
Broliden, K., Haase, A.T., Ahuja, S.K., Shearer, G.M., Andersson, J., Introduction: Back to basics: Mucosal immunity and novel HIV vaccine concepts (2009) J. Intern. Med., 265, pp. 5-17; 
Celli, J., Gregor, B., Turner, B., Afdhal, N.H., Bansil, R., Erramilli, S., Viscoelastic properties and dynamics of porcine gastric mucin (2005) Biomacromolecules, 6, pp. 1329-1333; 
Hong, Z., Chasan, B., Bansil, R., Turner, B.S., Bhaskar, K.R., Afdhal, N.H., Atomic force microscopy reveals aggregation of gastric mucin at low pH (2005) Biomacromolecules, 6, pp. 3458-3466; 
Maleki, A., Lafitte, G., Kjoniksen, A.L., Thuresson, K., Nystrom, B., Effect of pH on the association behavior in aqueous solutions of pig gastric mucin (2008) Carbohydr. Res., 343, pp. 328-340; 
Bansil, R., Turner, B.S., Mucin structure, aggregation, physiological functions and biomedical applications (2006) Curr. Opin. Colloid Interface Sci., 11, pp. 164-170; 
Katz, D.F., Dunmire, E.N., Cervical mucus: Problems and opportunities for drug delivery via the vagina and cervix (1993) Adv. Drug Delivery Rev., 11, pp. 385-401; 
Lieleg, O., Ribbeck, K., Biological hydrogels as selective diffusion barriers (2011) Trends Cell Biol., 21, pp. 543-551; 
Vladescu, I., Lieleg, O., Jang, S., Ribbeck, K., An adsorption chromatography assay to probe bulk particle transport through hydrogels (2012) J. Pharm. Sci., 101, pp. 436-442; 
Ponchel, G., Montisci, M.J., Dembri, A., Durrer, C., Duch{\^e}ne, D., Mucoadhesion of colloidal particulate systems in the gastro-intestinal tract (1997) Eur. J. Pharm. Biopharm., 44, pp. 25-31; 
Sakloetsakun, D., Perera, G., Hombach, J., Millotti, G., Bernkop-Schn{\"u}rch, A., The impact of vehicles on the mucoadhesive properties of orally administrated nanoparticles: A case study with chitosan-4-thiobutylamidine conjugate (2010) AAPS PharmSciTech, 11, pp. 1185-1192
},
	month = {2012///},
	pages = {3347 - 3356},
	abstract = {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. {\textcopyright} 2012 American Chemical Society.},
	keywords = {microbicides, mucin, mucoadhesion, mucosal drug delivery, particle tracking, rheology},
	isbn = {15438384 (ISSN)},
	url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84868526145\&partnerID=40\&md5=bd161f1b2ce30fba31c7a482dbe60b86},
	author = {Das Neves, J. and Rocha, C.M.R. and Gon{\c c}alves, M.P. and Carrier, R.L. and Amiji, M. and Bahia, M.F. and Sarmento, B.}
}
