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.

The in vitro and in vivo anti-tumor effect of layered double hydroxides nanoparticles as delivery for podophyllotoxin

“…(Xue et al, 2007). The purpose of this study was to investigate in vitro and vivo anti-tumor efficiency of LDH as PPT delivery.…”

The in vitro sustained release profile and antitumor effect of etoposide-layered double hydroxide nanohybrids

“…28,34 First, Tyr-LDH was prepared via the coprecipitation method under a nitrogen (N 2 ) atmosphere, as is conventional to minimize or avoid contamination by atmospheric CO 2 .…”

“…Special interests have focused on exploring the possibilities of using LDH drug delivery systems to deliver antiinflammatory drugs, 31 anticoagulants like heparin, 32 or anticancer drugs. 33,34 These studies involve some basic issues, including the intercalation (loading) of drugs or biomolecules into the LDH interlayer, the release behaviors of drugs or biomolecules from the LDH interlayer under different physiological conditions, the toxicity of LDH materials to cells, the cellular uptake of LDH nanoparticles, and cellular drug delivery tests. Furthermore, this drug delivery system can be modified to target specific cells or organs, thereby expanding its application range.…”

Improvement of pharmacokinetic and antitumor activity of layered double hydroxide nanoparticles by coating with PEGylated phospholipid membrane

“…12 Many studies have demonstrated that anticancer drugs [13][14][15][16] and genes 7,[17][18][19][20] could be successfully intercalated into the LDH layers. They can efficiently enter cells via the clathrin-mediated endocytosis pathway, which is the most common energydependent endocytosis.…”