Abstract

There is an urgent need for the development of alternative strategies for effective drug delivery to improve the outcome of patients suffering from deadly diseases such as cancer. Nanoparticles, in particular layered double hydroxide (LDH) nanoparticles, have great potential as nanocarriers of chemotherapeutic molecules. In this study, we synthesized (Zn, Al)-LDH nanoparticles and report their enhanced pH-dependent stability in comparison to the commonly used (Mg, Al)-LDH nanoparticles. Fluorescein isothiocyanate (FITC) and valproate (VP) were intercalated into (Zn, Al)-LDH nanoparticles to study cellular uptake, biocompatibility, and drug delivery capabilities using cultured pancreatic adenocarcinoma BxPC3 cells. Fluorescence measurements indicated that FITC-intercalated LDH nanoparticles showed a greater degree of energy-dependent uptake rather than passive uptake by BxPC3 cells, especially at high concentrations of nanoparticles. Tetrazolium-based colorimetric assays indicated that BxPC3 cells treated with VP-intercalated LDH nanoparticles showed a significant reduction in cell viability along with about 30-fold reduction in IC50compared to the drug alone. In contrast, the non-drug-intercalated LDH nanoparticles did not affect the cell viability indicating very low innate cytotoxicity. Our research indicates that the superior properties of (Zn, Al)-LDH nanoparticles make them ideal candidates for further development asin vivochemotherapy drug delivery agents.

Highlights

  • Conventional chemotherapeutic strategies involve administration of drugs by oral ingestion or intravenous injection

  • We report the synthesis, characterization, and in vitro drug delivery capabilities of layered double hydroxide (LDH) nanoparticles based on zinc and aluminum [(Zn, Al)-LDH] as more desirable drug delivery nanocarrier candidates than (Mg, Al)LDH NPs, which have been ubiquitously reported in the literature

  • To ensure that (Mg, Al, NO3)LDH and (Zn, Al, NO3)-LDH nanoparticles used for the aqueous stability study are suitable for biomedicine, transmission electron microscopy (TEM) was first used to characterize the morphology and particle size

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Summary

Introduction

Conventional chemotherapeutic strategies involve administration of drugs by oral ingestion or intravenous injection. This typically results in a systemic distribution of the drugs throughout the body with only 10–100 parts per million reaching the desired sites, while the associated secondary effects caused by the rest of the drugs can be serious and sometimes life-threatening. An ideal nanocarrier should encapsulate high doses of drugs, remain stable under physiological conditions, protect the drugs from degradation during the transport in the body, and release the drug intracellularly; its surface should remain stable and allow the conjugation of targeting moieties to increase the specificity and effectiveness of being uptaken by cancer cells; after biodegradation, the breakdown products should be biocompatible. Stability in physiological conditions, controlled release, and stimuliresponsive triggered drug release still remain challenging for nanocarrier development

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