Abstract

Layered Double Hydroxides (LDHs)-based drug delivery systems have, for many years, shown great promises for the delivery of chemical therapeutics and bioactive molecules to mammalian cells in vitro and in vivo. This system offers high efficiency and drug loading density, as well as excellent protection of loaded molecules from undesired degradation. Toxicological studies have also found LDHs to be biocompatible compared with other widely used nanoparticles, such as iron oxide, silica, and single-walled carbon nanotubes. A plethora of bio-molecules have been reported to either attach to the surface of or intercalate into LDH materials through co-precipitation or anion-exchange reaction, including amino acid and peptides, ATPs, vitamins, and even polysaccharides. Recently, LDHs have been used for gene delivery of small molecular nucleic acids, such as antisense, oligonucleotides, PCR fragments, siRNA molecules or sheared genomic DNA. These nano-medicines have been applied to target cells or organs in gene therapeutic approaches. This review summarizes current progress of the development of LDHs nanoparticle drug carriers for nucleotides, anti-inflammatory, anti-cancer drugs and recent LDH application in medical research. Ground breaking studies will be highlighted and an outlook of the possible future progress proposed. It is hoped that the layered inorganic material will open up new frontier of research, leading to new nano-drugs in clinical applications.

Highlights

  • Layered Double Hydroxides (LDHs), known as hydrotalcite-like (HTI), hydrotalcite-type (HTt) or anionic clays belong to a big family of layered materials [1]

  • Given that the clathrin-mediated endocytosis is the most common internalization pathway in all mammalian cells, the LDH nanoparticle might be able to pass through all type of cells membrane, suggesting its high cell penetration capability as drug delivery system

  • These results showed that the siRNA/LDH could achieve a faster and more effective target gene knockdown with less functioning time, suggesting that the LDH drug delivery system possessed higher membrane-penetrating and drug controlled-releasing efficiency in vitro

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Summary

Introduction

Layered Double Hydroxides (LDHs), known as hydrotalcite-like (HTI), hydrotalcite-type (HTt) or anionic clays belong to a big family of layered materials [1]. A unique property, which makes them diverse from other cationic-layered materials, is that they are capable of recovering the double-layered structure after thermal decomposition under mild conditions [10]. All these properties, such as high chemical versatility, anionic exchange capacity, and low cytotoxicity, are leading to a promising future in drug delivery and release, opening up wide possibilities for researches and development for its clinical application. Recently LDHs have been employed for clinical disease diagnosis, chemical industry and as a drug carrier responsible for delivering therapeutic and bioactive molecules such as peptides, anti-inflammatory drugs, and even small nucleic acids to mammalian cells in vitro or in vivo with the purpose of crossing the cell membrane into the cytoplasm [14,15,16]

Gene Delivery Overview
Small Nucleotide Intercalation with LDH Nanoparticles
Large Nucleotides Intercalation with LDH Nanoparticles
The LDH Application with Fenbufen
The Delivery of Anti-Cancer Drugs
The Delivery of Camptothecin and Podophyllotoxin
Recent Applications of LDHS in Medicine
Findings
Conclusions and Future Directions
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