Bio-Resorbable Nanoceramics for Gene and Drug Delivery
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Bio-Resorbable
Nanoceramics for Gene and Drug Delivery
Waltraud M. Kriven, Seo-Young Kwak, Matthew A. Wallig, and Jin-Ho Choy Abstract Nanoscale ceramic particles, such as layered double hydroxides (LDHs), have been developed to deliver drugs or genes into biological cells. In this article, we describe the controlled-release properties of LDHs as drug delivery carriers, the formation of bio-LDH nanohybrids, their in vivo and in vitro cytotoxicity tests, and their potential as anticancer gene delivery carriers. Unstable biomolecules can be intercalated into LDHs, displacing the interlayer anions; the drug or gene’s negative charge is thus shielded, enabling penetration into the cell. In the slightly acidic environment of the cell, ceramic nanoplatelets of 100 nm diameter dissolve, thus releasing the intercalates in a controlled manner. Keywords: biomedical materials, ceramics, drug delivery, intercalation, nonviral vectors, safety studies, scanning electron microscopy (SEM), transmission electron microscopy (TEM).
Introduction Thousands of years ago, humans discovered that clay could be irreversibly transformed by fire into ceramic pottery. Ceramic pots stored grains for long periods of time with minimal deterioration. Impervious ceramic vessels were watertight and fire-resistant, which allowed new forms of cooking. This discovery was a significant factor in the transformation of human culture from nomadic hunters to agrarian settlers. During the last few decades, another revolution has occurred in the use of ceramics by reducing their size to the nanometer level and enabling them to be applied to biosystems. Recently, many studies on hybridization between DNA and inorganic materials have appeared in the literature. For example, Au nanocrystals derivatized with complementary single-stranded DNA molecules (ssDNAs) can be hybridized with each other to form periodic arrays.1 The concept of using DNA as a framework for the precise spatial arrangement of molecular
MRS BULLETIN/JANUARY 2004
devices2 has recently been applied to the assembly of supramolecular aggregates from DNA-derivatized gold colloids.3,4 Such defined arrangements of nanocrystalline metal clusters (quantum dots) are being investigated for their new material properties, which may have applications in the field of laser technology.2 Another example is a study of the nature of DNA adsorption onto various substrates, such as mica, silylated mica, calcite, fluorite, and barite.5 Adsorption was explained using the electrostatic model. More recently, we have taken notice of inorganic layered double hydroxides (LDHs) with the composition M(II)1–xM(III)x (OH)2(An–)x/n · yH2O [where M(II) and M(III) are divalent and trivalent cations, A is the interlayer anion, and n is the charge on the interlayer anion], as candidate drug or gene delivery carriers. In this article, we describe the controlled-release properties of LDH as drug delivery carriers, the formation of bio-LDH nanohybrids, their in
vivo and in vitro cytotoxicity tests, and their potential as anti
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