title: Development and characterisation of ursolic acid nanocrystals without stabiliser having improved dissolution rate and in vitro anticancer activity.
abstract: Ursolic acid (UA), which is a natural pentacyclic triterpenoid, has the potential to be developed as an anticancer drug, whereas its poor aqueous solubility and dissolution rate limit its clinical application. The aim of the present study was to develop UA nanocrystals to enhance its aqueous dispersibility, dissolution rate and anticancer activity. Following the investigation on the effects of stabiliser, the ratio of organic phase to aqueous solution and drug concentration, the UA nanocrystals without stabiliser were successfully prepared by anti-solvent precipitation approach. The nanocrystals maintained similar crystallinity with particle size, polydispersion index and zeta potential values of 188.0 ± 4.4 nm, 0.154 ± 0.022, and -25.0 ± 5.9 mV, respectively. Compared with the raw material, the UA nanocrystals showed good aqueous dispensability and a higher dissolution rate, and they could be completely dissolved in 0.5% SDS solution within 120 min. Moreover, the suspension of UA nanocrystals was physically stable after storage at 4°C for 7 weeks. By inducing G2/M phase cell cycle arrest, the UA nanocrystals significantly induced stronger cell growth inhibition activity against MCF-7 cells compared with free drug in vitro, although the uptake of free UA was approximately twice higher than that of the UA nanocrystals. The UA nanocrystals may be used as a potential delivery formulation for intravenous injection with enhanced dissolution velocity and anticancer activity.
authors.forename: Ju
authors.initials: J
authors.lastname: Song
authors.forename: Yancai
authors.initials: Y
authors.lastname: Wang
authors.forename: Yuelin
authors.initials: Y
authors.lastname: Song
authors.forename: Hokman
authors.initials: H
authors.lastname: Chan
authors.forename: Chao
authors.initials: C
authors.lastname: Bi
authors.forename: Xiao
authors.initials: X
authors.lastname: Yang
authors.forename: Ru
authors.initials: R
authors.lastname: Yan
authors.forename: Yitao
authors.initials: Y
authors.lastname: Wang
authors.forename: Ying
authors.initials: Y
authors.lastname: Zheng
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D002626:Chemistry, Pharmaceutical / Q000379:methods; D016195:G2 Phase / Q000187:drug effects; D006801:Humans; D061986:MCF-7 Cells; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D012995:Solubility; D012997:Solvents / Q000737:chemistry; D013535:Suspensions / Q000737:chemistry / Q000494:pharmacology; D014315:Triterpenes / Q000737:chemistry* / Q000494:pharmacology*; D014867:Water / Q000737:chemistry; D000097245:Ursolic Acid
chemical_list: D000970:Antineoplastic Agents; D012997:Solvents; D013535:Suspensions; D014315:Triterpenes; D014867:Water; D000097245:Ursolic Acid
references.citation: Int J Pharm. 2013 Jan 30;441(1-2):261-8
references.pmid: 23194884
references.citation: Biosci Biotechnol Biochem. 2007 Jan;71(1):31-7
references.pmid: 17213663
references.citation: Eur J Pharm Biopharm. 2006 Jan;62(1):3-16
references.pmid: 16129588
references.citation: Drug Dev Ind Pharm. 2009 Mar;35(3):305-10
references.pmid: 18798089
references.citation: Int J Nanomedicine. 2012;7:1793-804
references.pmid: 22619528
references.citation: Toxicol In Vitro. 2011 Oct;25(7):1274-80
references.pmid: 21539908
references.citation: Arch Pharm Res. 1997 Jun;20(3):269-74
references.pmid: 18975163
references.citation: Biol Pharm Bull. 2012;35(7):1022-8
references.pmid: 22791147
references.citation: AAPS PharmSciTech. 2012 Dec;13(4):1436-45
references.pmid: 23070562
references.citation: Oncol Rep. 2012 Aug;28(2):501-10
references.pmid: 22641480
references.citation: Biochem Biophys Res Commun. 2012 Mar 23;419(4):741-7
references.pmid: 22387548
references.citation: Int J Pharm. 2012 Oct 15;436(1-2):815-24
references.pmid: 22846410
references.citation: Int J Pharm. 2006 Oct 12;323(1-2):153-60
references.pmid: 16828244
references.citation: Chin Med J (Engl). 2010 Jul;123(14):1915-23
references.pmid: 20819578
references.citation: Int J Nanomedicine. 2008;3(3):295-309
references.pmid: 18990939
references.citation: Cancer Invest. 2009 Aug;27(7):723-33
references.pmid: 19440893
references.citation: Cancer Lett. 2011 Aug 28;307(2):158-64
references.pmid: 21507570
references.citation: Int J Pharm. 2009 Jun 22;375(1-2):84-8
references.pmid: 19481693
references.citation: Adv Drug Deliv Rev. 2011 May 30;63(6):406-16
references.pmid: 21457742
references.citation: J Zhejiang Univ Sci B. 2009 Sep;10(9):668-74
references.pmid: 19735099
references.citation: J Ethnopharmacol. 1995 Dec 1;49(2):57-68
references.pmid: 8847885
references.citation: Int J Pharm. 2008 May 1;355(1-2):195-202
references.pmid: 18207676
references.citation: Eur J Pharm Biopharm. 2010 Aug;75(3):334-40
references.pmid: 20438840
references.citation: Adv Drug Deliv Rev. 2011 May 30;63(6):456-69
references.pmid: 21315781
references.citation: J Chromatogr A. 2004 Sep 17;1049(1-2):37-42
references.pmid: 15499915
references.citation: Eur J Pharm Biopharm. 2011 May;78(1):1-9
references.pmid: 21266197
references.citation: Int J Pharm. 2011 Aug 30;415(1-2):293-300
references.pmid: 21679755
references.citation: Pharm Res. 2011 Aug;28(8):2020-33
references.pmid: 21479757
references.citation: J Control Release. 2011 Jan 20;149(2):175-81
references.pmid: 20946923
references.citation: Small. 2011 May 23;7(10):1322-37
references.pmid: 21520409
references.citation: Eur J Pharm Sci. 2010 Jul 11;40(4):325-34
references.pmid: 20417274
references.citation: Med Oncol. 2012 Mar;29(1):10-5
references.pmid: 21191671