Natural Polysaccharides for siRNA Delivery: Nanocarriers Based on Chitosan, Hyaluronic Acid, and Their Derivatives

Abstract

Natural polysaccharides are frequently used in the design of drug delivery systems due to their biocompatibility, biodegradability, and low toxicity. Moreover, they are diverse in structure, size, and charge, and their chemical functional groups can be easily modified to match the needs of the final application and mode of administration. This review focuses on polysaccharidic nanocarriers based on chitosan and hyaluronic acid for small interfering RNA (siRNA) delivery, which are highly positively and negatively charged, respectively. The key properties, strengths, and drawbacks of each polysaccharide are discussed. In addition, their use as efficient nanodelivery systems for gene silencing applications is put into context using the most recent examples from the literature. The latest advances in this field illustrate effectively how chitosan and hyaluronic acid can be modified or associated with other molecules in order to overcome their limitations to produce optimized siRNA delivery systems with promising in vitro and in vivo results.

Staggered Herringbone Microfluid Device for the Manufacturing of Chitosan/TPP Nanoparticles: Systematic Optimization and Preliminary Biological Evaluation

“…CS is a non-toxic, biocompatible and biodegradable hydrophilic polymer with low immunogenicity that received FDA approval for wound dressings as well as in dietary application. In addition, the CS inherent antibacterial, antioxidant and mucoadhesive properties together with its capacity to transiently open epithelial tight junctions further enhance polymer versatility, making CS particularly suited for a variety of applications that include immunization and protein delivery [14], transmucosal and topical drug delivery [11,15], anti-cancer drug delivery [16], brain drug delivery [17] and gene delivery [18].…”

Inhaled RNA Therapy: From Promise to Reality

“…There are two main categories of polymers: natural and synthetic polymers. Natural polymers have the advantages of excellent biocompatibility, biodegradability, and safety profiles [ 42 ]. Derived from the shells of crustaceans, the natural polymer chitosan is commonly investigated for pulmonary delivery due to its mucoadhesive and mucopermeable properties, enabling it to cross the mucus layer in the airways efficiently [ 43 ].…”

Chitosan-Based Drug Delivery System: Applications in Fish Biotechnology

“…The addition of TPP was shown to reduce the particle size and increase the stability of complexes in biological fluids [19,[43][44][45][46][47]. The inclusion of hyaluronic acid in chitosan-siRNA polyplexes can be also a promising strategy to increase stability and targeting capacity, while lowering aggregation in the presence of serum proteins [48]. [3,31,32]; and the introduction of a quaternary ammonium salt group, which increases chargeability, mucoadhesion, crossing of mucus layers and binding to epithelial surfaces [6,33,34].…”

“…The addition of TPP was shown to reduce the particle size and increase the stability of complexes in biological fluids [19,[43][44][45][46][47]. The inclusion of hyaluronic acid in chitosan-siRNA polyplexes can be also a promising strategy to increase stability and targeting capacity, while lowering aggregation in the presence of serum proteins [48]. One major advantage of chitosan is that chitosan-DNA complexation protects DNA from DNase-mediated degradation, possibly as a result of modification of the DNA tertiary structure [20,49].…”

“…After unpacking, siRNA/miRNA associates with RNA-induced silencing complex (RISC) in the cytosol. The RNAi-guided complex hybridizes with target mRNA, leading to mRNA cleavage and/or translation repression, and subsequent inhibition of protein synthesis [9,10,48,79]. The use of shRNA expression plasmids allowing long lasting expression of siRNA may improve RNAi in vivo.…”