Chitosan/TPP-Hyaluronic Acid Nanoparticles: A New Vehicle for Gene Delivery to the Spinal Cord

Abstract

Gene delivery offers therapeutic promise for the treatment of neurological diseases and spinal cord injury. Several studies have offered viral vectors as vehicles to deliver therapeutic agents, yet their toxicity and immunogenicity, along with the cost of their large-scale formulation, limits their clinical use. As such, non-viral vectors are attractive in that they offer improved safety profiles compared to viruses. Poly(ethylene imine) (PEI) is one of the most extensively studied non-viral vectors, but its clinical value is limited y its cytotoxicity. Recently, chitosan/DNA complex nanoparticles have een considered as a vector for gene delivery. Here, we demonstrate that DNA nanoparticles made of hyaluronic acid (HA) and chitosan have low cytotoxicity and induce high transgene expression in neural stem cells and organotypic spinal cord slice tissue. Chitosan-TPP/HA nanoparticles were significantly less cytotoxic than PEI at various concentrations. Additionally, chitosan-TPP/HA nanoparticles with pDNA induced higher transgene expression in vitro for a longer duration than PEI in neural stem cells. These results suggest chitosan-TPP/HA nanoparticles may have the potential to serve as an option for gene delivery to the spinal cord.

Silencing tumor necrosis factor-alpha in vitro from small interfering RNA-decorated titanium nanotube array can facilitate osteogenic differentiation of mesenchymal stem cells

“…24,25 The CS/TPP-HA NPs have been recently proven to be a powerful vehicle for gene delivery, even to the spinal cord. 21,26 In our study, the NPs also showed significant knockdown efficiency. The TPP-HA is negatively charged, which could facilitate the NPs formation with positively charged …”

“…21 Briefly, chitosan (CS; 150 kDa, 95% deacetylation, MP Biomedicals, Santa Ana, CA, USA) was dissolved in hydrochloric acid (0.04 M) overnight at a concentration of 2 mg/mL. Tripolyphosphate (TPP) and sodium hyaluronate (HA, Mw ≈360 kDa) were dissolved in deionized water (pH 5.5) at a concentration of 1 mg/mL and filtered through a 0.22 µm pore size filter.…”

Overviews on the cellular uptake mechanism of polysaccharide colloidal nanoparticles

“…demonstrated that nanoparticles containing HA and TCS could be used as a powerful tool for gene delivery to spinal cord. It was shown that HA/CS nanoparticles are not cytotoxic and able to efficiently deliver pDNA into neuronal cell as a result of hyaluronan receptor mediation .…”

Microarc-oxidized titanium surfaces functionalized with microRNA-21-loaded chitosan/hyaluronic acid nanoparticles promote the osteogenic differentiation of human bone marrow mesenchymal stem cells

“…Gelatin powder Preparation of cs/ha/mir-21 nanoparticles CS/HA nanoparticles were produced as described previously. 20,23 In brief, CS was dissolved in 2% acetic acid at a concentration of 1% (w/v) (pH 5.5), and HA was dissolved in water at 0.1% (w/v) (pH 5.5). Both the CS and HA solutions were filtered through a 0.22 μm membrane and mixed at a rate of 3,000 rpm for 2 hours.…”

“…19 Nonviral gene-delivery systems, such as chitosan (CS)/hyaluronic acid (HA) nanoparticles, [20][21][22][23] have been proposed as safer alternatives to viral vectors due to their good biocompatibility, biodegradability, high stability, and minimal host immune response. 20 The positive charges of CS contribute to electrostatic interactions with negatively charged substances, which are also responsible for the capacity of CS to interact with the negatively charged cell surfaces. 24 HA is a natural, anionic polysaccharide that is naturally found in humans, and the natural biomineralization process of HA exerts vital functions in bone and tooth development.…”