Capacity of mesoporous bioactive glass nanoparticles to deliver therapeutic molecules

Abstract

Inorganic bioactive nanomaterials are attractive for hard tissue regeneration, including nanocomponents for bone replacement composites and nanovehicles for delivering therapeutics. Bioactive glass nanoparticles (BGn) have recently gained potential usefulness as bone and tooth regeneratives. Here we demonstrate the capacity of the BGn with mesopores to load and deliver therapeutic molecules (drugs and particularly genes). Spherical BGn with sizes of 80-90 nm were produced to obtain 3-5 nm sized mesopores through a sono-reacted sol-gel process. A simulated body fluid test of the mesoporous BGn confirmed their excellent apatite forming ability and the cellular toxicity study demonstrated their good cell viability up to 100 μg ml(-1). Small molecules like chemical drug (Na-ampicillin) and gene (small interfering RNA; siRNA) were introduced as model drugs considering the mesopore size of the nanoparticles. Moreover, amine-functionalization allowed switchable surface charge property of the BGn (from -20-30 mV to +20-30 mV). Loading of ampicillin or siRNA saturated within a few hours (~2 h) and reflected the mesopore structure. While the ampicillin released relatively rapidly (~12 h), the siRNA continued to release up to 3 days with almost zero-order kinetics. The siRNA-nanoparticles were easily taken up by the cells, with a transfection efficiency as high as ~80%. The silencing effect of siRNA delivered from the BGn, as examined by using bcl-2 model gene, showed dramatic down-regulation (~15% of control), suggesting the potential use of BGn as a new class of nanovehicles for genes. This, in conjunction with other attractive properties, including size- and mesopore-related high surface area and pore volume, tunable surface chemistry, apatite-forming ability, good cell viability and the possible ion-related stimulatory effects, will potentiate the usefulness of the BGn in hard tissue regeneration.

Inhibition of osteoclastogenesis through siRNA delivery with tunable mesoporous bioactive nanocarriers

“…The cytotoxicity of the inert mesoporous nanomaterials is generally influenced by numerous factors including particle size, pore size, and surface chemistry [60,71,72]. The cell viability of both MBG nanocarriers was observed to be dose-and time-dependent.…”

“…The internal mesoporous characteristics of MBG are similar to those of other MSNs, but their major advantage is their bonebioactivity related to ionic release as well as their degradability [55][56][57][58]. In our recent studies, MBG have shown a high level of mesoporosity for loading and sustained release of biomolecules, including chemical drugs and genes [59][60][61]. In addition, MBG allowed intracellular uptake via endocytosis without cell or tissue damage [60].…”

“…In our recent studies, MBG have shown a high level of mesoporosity for loading and sustained release of biomolecules, including chemical drugs and genes [59][60][61]. In addition, MBG allowed intracellular uptake via endocytosis without cell or tissue damage [60]. Along with their capacity to deliver therapeutic molecules, MBG can also be used for repair and regeneration of hard tissues, like tooth and bone, due to their intrinsic bone-bioactive nature either in a native form or in combination with scaffolding matrices [55][56][57][58].…”

ZnO quantum dots modified bioactive glass nanoparticles with pH-sensitive release of Zn ions, fluorescence, antibacterial and osteogenic properties

“…growth factors and anticancer drugs), owing to the small particle size, for specific intended purposes. 4,5 The incorporation of biomolecules in bioceramics or bioactive glasses (BG) can enhance the therapeutic effects of the materials in bone regeneration 6 or anticancer treatments. 5 However, the relatively short shelf-life, the sensitivity to outer conditions, and the high cost of most biomolecules (e.g.…”

Applications of nanparticle based drug delivery systems in bone tissue engineering

“…The siRNA-nanoparticles were also easily taken up by the cells with a transfection efficiency of up to 80 %. It may be a promising drug release system in bone tissue regeneration [48].…”