title: Efficacy of local delivery of ardipusilloside I using biodegradable implants against cerebral tumor growth.
abstract: Ardipusilloside I (ADS-I) is a natural compound that can be isolated from the Chinese medicinal herb Ardisiapusilla A.DC, and has been reported to inhibit the growth of glioblastoma cells in cultures. This study was designed to test its efficacy by the delivery using biodegradable implants against glioblastoma in vivo. ADS-I was incorporated into polymer microspheres, which were prepared by a mixture of poly (D, L-lactic acid) and poly (D, L-lactic-co-glycolic acid) polymers and then fabricated into wafers. The anti-glioma activities of ADS-I-loaded wafers were examined by methylthiazol tetrazolium (MTT) assay in cultured rat C6 glioma cells, and by magnetic resonance imaging (MRI) and survival monitoring in C6 glioma-bearing rats. Here, we showed that ADS-I-loaded wafers sustained ADS-I release in vitro for 36 days in Higuchi model of kinetics, and had the same cytotoxic activity as ADS-I in the solution against the growth of C6 glioma cells in cultures. In C6 glioma-bearing rats, ADS-I wafer implants inhibited tumor growth in a dose-dependent matter, and were more effective than the same dosage of ADS-I in the solution. The tumor suppression efficacies of ADS-I wafer implants were positively correlated with an increase in tumor cell apoptosis and prolonged animal survival, and were associated with a decrease in vascular endothelial growth factor, C-reactive protein, tumor necrosis factor-α and interleukin-6, and an increase in interleukin-2 expression. In conclusion, this study demonstrates significant efficacy of local delivery of ADS-I using polymer implants against glioma tumor growth in vivo, suggesting the potential of ADS-I-loaded wafers for glioma treatment.
authors: State Key Laboratory of Military Stomatology, Department of Pharmacy, School of Stomatology, The Fourth Military Medical University Xi'an, Shaanxi 710032, China.
authors: Huan
authors: H
authors: Dang
authors: State Key Laboratory of Military Stomatology, Department of Pharmacy, School of Stomatology, The Fourth Military Medical University Xi'an, Shaanxi 710032, China.
authors: Ji
authors: J
authors: Wang
authors: Department of Pharmacy, Shaanxi University of Chinese Medicine Xianyang, Shaanxi 712046, China.
authors: Jiang-Xue
authors: JX
authors: Cheng
authors: State Key Laboratory of Military Stomatology, Department of Pharmacy, School of Stomatology, The Fourth Military Medical University Xi'an, Shaanxi 710032, China.
authors: Peng-Yuan
authors: PY
authors: Wang
authors: State Key Laboratory of Military Stomatology, Department of Pharmacy, School of Stomatology, The Fourth Military Medical University Xi'an, Shaanxi 710032, China.
authors: Ying
authors: Y
authors: Wang
authors: State Key Laboratory of Military Stomatology, Department of Pharmacy, School of Stomatology, The Fourth Military Medical University Xi'an, Shaanxi 710032, China.
authors: Li-Fei
authors: LF
authors: Cheng
authors: Department of Urologic Sciences, The University of British Columbia Vancouver, BC, Canada ; Immunity and Infection Research Centre, Vancouver Coastal Health Research Institute Vancouver, BC, Canada.
authors: Caigan
authors: C
authors: Du
authors: State Key Laboratory of Military Stomatology, Department of Pharmacy, School of Stomatology, The Fourth Military Medical University Xi'an, Shaanxi 710032, China.
authors: Xiao-Juan
authors: XJ
authors: Wang
keywords: Ardipusilloside I; anti-tumor activities; glioblastoma; implant wafer; interstitial therapy
references: Phytomedicine. 2012 May 15;19(7):603-8
references: 22349030
references: J Neurooncol. 2012 Aug;109(1):35-44
references: 22528800
references: Annu Rev Chem Biomol Eng. 2010;1:149-73
references: 22432577
references: J Neurooncol. 2011 Mar;102(1):35-41
references: 20607353
references: J Asian Nat Prod Res. 2012;14(1):55-63
references: 22263594
references: Pharm Res. 2002 Apr;19(4):546-50
references: 12033393
references: J Neurooncol. 2002 Jan;56(1):13-9
references: 11949822
references: Eur J Pharm Biopharm. 2005 Jan;59(1):169-75
references: 15567315
references: Anticancer Res. 2014 Jan;34(1):339-47
references: 24403485
references: Biomaterials. 2014 Feb;35(7):2374-82
references: 24342723
references: Cancer Res. 1979 Feb;39(2 Pt 1):542-4
references: 83910
references: Cancer Gene Ther. 2005 Oct;12(10):835-48
references: 15891772
references: Mol Biol Cell. 1993 Jan;4(1):121-33
references: 7680247
references: Environ Toxicol Pharmacol. 2009 Mar;27(2):264-70
references: 21783950
references: J Neurooncol. 2003 Jul;63(3):225-31
references: 12892228
references: Cancer Epidemiol. 2013 Oct;37(5):697-702
references: 23870768
references: Science. 1984 Jun 22;224(4655):1312-6
references: 6427923
references: J Cell Biochem. 1994 Jan;54(1):56-66
references: 8126087
references: Nature. 1992 Oct 29;359(6398):845-8
references: 1279432
references: J Mater Sci Mater Med. 2010 May;21(5):1563-71
references: 20221788
references: Phytomedicine. 2010 Jun;17(7):519-26
references: 20149613
references: Int J Mol Sci. 2011;12(3):1684-96
references: 21673916
references: J Cancer Res Clin Oncol. 2013 Dec;139(12):1995-2003
references: 24072231
references: Life Sci. 2014 Aug 6;110(1):15-22
references: 24984215
references: Planta Med. 2012 Apr;78(6):565-74
references: 22307936
references: J Microencapsul. 2011;28(1):46-54
references: 21171816
references: J Cell Mol Med. 2013 Oct;17(10):1218-35
references: 23998913
references: AAPS PharmSciTech. 2013 Jun;14 (2):880-9
references: 23653087
references: Science. 1988 May 27;240(4856):1169-76
references: 3131876
references: Int J Pharm. 2011 May 16;409(1-2):289-96
references: 21356295
references: J Microencapsul. 2009 Feb;26(1):18-26
references: 18465288
references: Mol Pharm. 2011 Aug 1;8(4):1332-41
references: 21707071
references: Mediators Inflamm. 2013;2013:979748
references: 23864770
references: BMC Complement Altern Med. 2013 Nov 21;13:322
references: 24256941