Chitosan-based formulations for delivery of DNA and siRNA. Adv Drug Deliv Rev

School of Pharmacy, Shenyang Pharmaceutical University, 110016 Shenyang, China.
Advanced drug delivery reviews (Impact Factor: 15.04). 09/2009; 62(1):12-27. DOI: 10.1016/j.addr.2009.08.004
Source: PubMed


Among non-viral vectors, chitosan and chitosan derivatives have been developed in vitro and in vivo for DNA and siRNA delivery systems because of their cationic charge, biodegradability and biocompatibility, as well as their mucoadhesive and permeability-enhancing properties. However, the transfection efficiency of chitosan is too low for clinical application. Studies indicated that the transfection efficiency depends on a series of chitosan-based formulation parameters, such as the Mw of chitosan, its degree of deacetylation, the charge ratio of chitosan to DNA/siRNA (N/P ratio), the chitosan salt form used, the DNA/siRNA concentration, pH, serum, additives, preparation techniques of chitosan/nucleic acid particles and routes of administration. In this paper, chitosan-based formulations for the delivery of DNA and siRNA were reviewed to facilitate the process of chitosan vector development for clinical application. In addition to formulation optimization, chitosan structure modification or additive incorporation is an effective way to improve the stability of the polyplex in biological fluids, enhance targeted cell delivery and facilitate endo-lysosomal release of the complex. In summary, the transfection efficiency of chitosan-based delivery systems can be adjusted by changing formulation-related parameters.

Download full-text


Available from: Shirui Mao, Dec 15, 2015
  • Source
    • "Therefore, the success of nucleic acid-based therapeutics is largely dependent on the development of safe and efficient vectors which allow their delivery to the suitable cellular compartment of target cells. A diverse range of materials have been explored to address key challenges of in vivo nucleic acid delivery, which includes cationic lipids [25,26,118], peptides [31,119], cationic polymers [27,29,30,120], aptamers [121], and antibodies [122,123]. Among them, polymeric vectors have received increasing interest for nucleic acid delivery since they could be chemically modified to ensure high intracellular deposition. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Gene therapy is an emerging therapeutic strategy for the cure or treatment of a spectrum of genetic disorders. Nevertheless, advances in gene therapy are immensely reliant upon design of an efficient gene carrier that can deliver genetic cargoes into the desired cell populations. Among various nonviral gene delivery systems, chitosan-based carriers have gained increasing attention because of their high cationic charge density, excellent biocompatibility, nearly nonexistent cytotoxicity, negligible immune response, and ideal ability to undergo chemical conjugation. However, a major shortcoming of chitosan-based carriers is their poor cellular uptake, leading to inadequate transfection efficiency. The intrinsic feature of cell penetrating peptides (CPPs) for transporting diverse cargoes into multiple cell and tissue types in a safe manner suggests that they can be conjugated to chitosan for improving its transfection efficiency. In this review, we briefly discuss CPPs and their classification, and also the major mechanisms contributing to the cellular uptake of CPPs and cargo conjugates. We also discuss immense improvements for the delivery of nucleic acids using CPP-conjugated chitosan-based carriers with special emphasis on plasmid DNA and small interfering RNA.
    Preview · Article · Dec 2015 · International Journal of Molecular Sciences
    • "The chitosan-DNA nanoparticles were prepared following the method described by Mao et al. (2010). Briefly, high molecular weight chitosan (150 kDa) was dissolved in 1% acetic acid (w/v) and 0.1 M NaNO 2 was dropped into it until the chitosan/NaNO 2 ratio of 0.01 was reached. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Cyprinus carpio (koi) is one of the most popular ornamental fish. A major problem for C. carpio farming is bacterial infections especially by Aeromonas hydrophila. Previously studies had shown that the Phagocytosis Activating Protein (PAP) gene was involved in the innate immune response of animals. Therefore, we attempted to identify a role for the PAP gene in the immunology of C. carpio. The expression of the PAP was found in C. carpio whole blood and increased when the fish were stimulated by inactivated A. hydrophila. In addition, PAP-phMGFP DNA was injected as an immunostimulant. The survival rate and the phagocytic index were significantly increased in the A. hydrophila infected fish that received the PAP-phMGFP DNA immunostimulant. A chitosan-PAP-phMGFP nanoparticle was then developed and feeded into fish which infected with A. hydrophila. These fish had a significantly lower mortality rate than the control. Therefore, this research confirmed a key role for PAP in protection fish from bacterial infection and the chitosan-PAP-phMGFP nanoparticle could be a good prototype for fish immunostimulant in the future.
    No preview · Article · Dec 2015 · Developmental and comparative immunology
    • "Its positive charge promotes electrostatic interactions between the pSiNP and negatively charged oligonucleotides and cell membranes, facilitating both the loading of particles and uptake of the nanocarrier into the cell interior [38]. Chitosan has several interesting features relevant to drug delivery applications [14] [37] [39] [40], including its mucoadhesive properties which enhance mucosal penetration. Previously, Wu and Sailor [41] used chitosan hydrogel to cap porous silicon dioxide films in order to provide a pH-responsive insulin release. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Porous silicon nanoparticles (pSiNPs) are a promising nanocarrier system for drug delivery owing to their biocompatibility, biodegradability, and non-inflammatory nature. Here, we investigate the fabrication and characterization of thermally hydrocarbonized pSiNPs (THCpSiNPs) and chitosan-coated THCpSiNPs for therapeutic oligonucleotide delivery. Chitosan coating after oligonucleotide loading significantly improves sustained oligonucleotide release and suppresses burst release effects. Moreover, cellular uptake, endocytosis, and cytotoxicity of oligonucleotide-loaded THCpSiNPs have been evaluated in vitro. Standard cell viability assays demonstrate that cells incubated with the NPs at a concentration of 0.1 mg/mL are 95% viable. In addition, chitosan coating significantly enhances the uptake of oligonucleotide-loaded THCpSiNPs across the cell membrane. Moreover, histopathological analysis of liver, kidney, spleen, and skin tissue collected from mice receiving NPs further demonstrates the biocompatible and non-inflammatory properties of the NPs as a gene delivery vehicle for intravenous and subcutaneous administration in vivo. Taken together, these results suggest that THCpSiNPs provide a versatile platform that could be used as efficient vehicles for the intracellular delivery of oligonucleotides for gene therapy.
    No preview · Article · Apr 2015 · Nano Research
Show more