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Particle size tailoring of ursolic acid nanosuspensions for improved anticancer activity by controlled antisolvent precipitation
Wang Y.4; Song J.4; Chow S.F.2; Chow A.H.L.2; Zheng Y.4
2015-10-15
Source PublicationInternational Journal of Pharmaceutics
ISSN18733476 03785173
Volume494Issue:1Pages:479-489
Abstract

The present study was aimed at tailoring the particle size of ursolic acid (UA) nanosuspension for improved anticancer activity. UA nanosuspensions were prepared by antisolvent precipitation using a four-stream multi-inlet vortex mixer (MIVM) under defined conditions of varying solvent composition, drug feeding concentration or stream flow rate. The resulting products were characterized for particle size and polydispersity. Two of the UA nanosuspensions with mean particle sizes of 100 and 300 nm were further assessed for their in-vitro activity against MCF-7 breast cancer cells using fluorescence microscopy with 4′,6-diamidino-2-phenylindole (DAPI) staining, as well as flow cytometry with propidium (PI) staining and with double staining by fluorescein isothiocyanate. It was revealed that the solvent composition, drug feeding concentration and stream flow rate were critical parameters for particle size control of the UA nanosuspensions generated with the MIVM. Specifically, decreasing the UA feeding concentration or increasing the stream flow rate or ethanol content resulted in a reduction of particle size. Excellent reproducibility for nanosuspension production was demonstrated for the 100 and 300 nm UA preparations with a deviation of not more than 5% in particle size from the mean value of three independent batches. Fluorescence microscopy and flow cytometry revealed that these two different sized UA nanosuspensions, particularly the 300 nm sample, exhibited a higher anti-proliferation activity against the MCF-7 cells and afforded a larger population of these cells in both early and late apoptotic phases. In conclusion, MIVM is a robust and pragmatic tool for tailoring the particle size of the UA nanosuspension. Particle size appears to be a critical determinant of the anticancer activity of the UA nanoparticles.

KeywordAntisolvent Nanoprecipitation Breast Cancer In-vitro Anticancer Activity Multi-inlet Vortex Mixer (Mivm) Nanoparticles Ursolic Acid
DOI10.1016/j.ijpharm.2015.08.052
URLView the original
Indexed BySCI
Language英语
WOS Research AreaPharmacology & Pharmacy
WOS SubjectPharmacology & Pharmacy
WOS IDWOS:000361649300050
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被引频次[WOS]:19   [WOS记录]     [WOS相关记录]
Document TypeJournal article
专题Institute of Chinese Medical Sciences
Affiliation1.Beijing Aohe Pharmaceutical Research Institute Co. Ltd.
2.Chinese University of Hong Kong
3.Qilu University of Technology
4.Universidade de Macau
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Wang Y.,Song J.,Chow S.F.,et al. Particle size tailoring of ursolic acid nanosuspensions for improved anticancer activity by controlled antisolvent precipitation[J]. International Journal of Pharmaceutics,2015,494(1):479-489.
APA Wang Y.,Song J.,Chow S.F.,Chow A.H.L.,&Zheng Y..(2015).Particle size tailoring of ursolic acid nanosuspensions for improved anticancer activity by controlled antisolvent precipitation.International Journal of Pharmaceutics,494(1),479-489.
MLA Wang Y.,et al."Particle size tailoring of ursolic acid nanosuspensions for improved anticancer activity by controlled antisolvent precipitation".International Journal of Pharmaceutics 494.1(2015):479-489.
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