title: The construction and characterization of layered double hydroxides as delivery vehicles for podophyllotoxins.
abstract: The aim of this study was to construct PPT-LDH nanohybrids and compare their tumor inhibition effects with that of free PPT. Anticancer drug podophyllotoxin (PPT) was encapsulated in the galleries of Mg-Al layered double hydroxides (LDHs) by a two-step approach. Tyrosine (Tyr) was first incorporated into the interlayer space by co-precipitation with LDH, prop-opening the layers of Mg-Al/LDH and creating an interlayer environment inviting drug molecules. PPT was subsequently intercalated into the resulting material lamella by an ion exchange process. The intermediate and final products, which can be termed drug-inorganic nanocomposites, have been characterized by powder X-ray diffraction (XRD), UV-VIS spectrophotometer, transmission electron microscopy (TEM) and in cell culture. Our results demonstrate that the interlayer spacing distance of the PPT-LDH nanohybrids (34% w/w of drug/material) is 18.2 A. LDHs do not harm normal cells (293T) based on toxicity tests. Ex-vivo anticancer experiments reveal that the PPT-LDH nanohybrids have higher tumor suppression effects than intercalated PPT. We conclude that the higher tumor inhibition effects of PPT-LDH hybrids result from the inorganic drug delivery vehicle, LDHs.
authors: School of Life Science and Technology, Tongji University, Shanghai 200092, China.
authors: Yan Hua
authors: YH
authors: Xue
authors: Rui
authors: R
authors: Zhang
authors: Xiao Yu
authors: XY
authors: Sun
authors: Shi Long
authors: SL
authors: Wang
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000493:pharmacokinetics; D006801:Humans; D006878:Hydroxides / Q000737:chemistry*; D049329:Nanostructures / Q000737:chemistry; D014677:Pharmaceutical Vehicles / Q000138:chemical synthesis* / Q000737:chemistry; D011034:Podophyllotoxin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D003692:Delayed-Action Preparations; D006878:Hydroxides; D014677:Pharmaceutical Vehicles; D011034:Podophyllotoxin
references: Biomaterials. 2004 Jul;25(15):3059-64
references: 14967539
references: Pharm Res. 1989 May;6(5):408-12
references: 2748532
references: J Pharm Sci. 2005 May;94(5):1135-48
references: 15793807
references: Hum Gene Ther. 1995 Sep;6(9):1129-44
references: 8527471
references: Biochimie. 1998 Mar;80(3):207-22
references: 9615861
references: Angew Chem Int Ed Engl. 2000 Nov 17;39(22):4041-4045
references: 11093198
references: Pharm Res. 1993 Jul;10(7):998-1004
references: 8378263
references: J Clin Oncol. 1985 May;3(5):666-71
references: 2582097
references: Pharmazie. 1988 Apr;43(4):249-51
references: 3413211
references: J Natl Cancer Inst. 1988 Dec 7;80(19):1526-33
references: 2848132
references: Cancer. 1991 Jan 1;67(1 Suppl):319-29
references: 1984835
references: Int J Pharm. 2004 Jan 28;269(2):469-78
references: 14706258
references: Int J Pharm. 2001 Jun 4;220(1-2):23-32
references: 11376964
references: Trends Biotechnol. 1997 Jun;15(6):217-24
references: 9183864
references: J Control Release. 2004 Mar 24;95(3):501-14
references: 15023461