Chitosan Nanoparticles for Plasmid DNA Delivery: Effect of Chitosan Molecular Structure on Formulation and Release Characteristics
Faculty of Pharmacy , Ankara University, Engüri, Ankara, Turkey Drug Delivery
(Impact Factor: 2.56).
03/2004; 11(2):107-12. DOI: 10.1080/10717540490280705
Chitosan can be useful as a nonviral vector for gene delivery. Although there are several reports to form chitosan-pDNA particles, the optimization and effect on transfection remain insufficient. The chitosan-pDNA nanoparticles were formulated using complex coacervation and solvent evaporation techniques. The important parameters for the encapsulation efficiency were investigated, including molecular weight and deacetylation degree of chitosan. We found that encapsulation efficiency of pDNA is directly proportional with deacetylation degree, but there is an inverse proportion with molecular weight of chitosan. DNA-nanoparticles in the size range of 450-820 nm depend on the formulation process. The surface charge of the nanoparticles prepared with complex coacervation method was slightly positive with a zeta potential of +9 to +18 mV; nevertheless, nanoparticles prepared with solvent evaporation method had a zeta potential approximately +30 mV. The pDNA-chitosan nanoparticles prepared by using high deacetylation degree chitosan having 92.7%, 98.0%, and 90.4% encapsulation efficiency protect the encapsulated pDNA from nuclease degradation as shown by electrophoretic mobility analysis. The release of pDNA from the formulation prepared by complex coacervation was completed in 24 hr whereas the formulation prepared by evaporation technique released pDNA in 96 hr, but these release profiles are not statistically significant compared with formulations with similar structure (p > .05). According to the results, we suggest nanoparticles have the potential to be used as a transfer vector in further studies.
Available from: Alireza Tahamtan
- "Amongst them, chitosan (CS) is a particularly attractive cationic vector derived from polysaccharides. Polysaccharides are the most abundant polymers in nature and CS exhibits desirable characteristics such as biocompatibility and biodegradability that is essential for gene delivery (Bozkir and Saka 2004). CS is also nonimmunogenic and nontoxic. "
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ABSTRACT: Chitosan nanoparticles (CS NPs) were prepared as a carrier for Human papillomavirus type 16 HPV-16) E7 gene and their gene transfection ability were evaluated in vitro. The plasmid expressing green fluorescent protein (pEGFP) was used as a reporter gene. Gel electrophoresis demonstrated full binding of CS NPs with the pDNA. The transfection of CS-pEGFP NPs was efficient in CHO cells and the expression of green fluorescent proteins was well observed. The expression of E7 proteins was confirmed under SDS-PAGE and western blot analysis. As a conclusion CS NPs may serve as an effective nonviral carrier for delivery of nucleotides into eukaryotic cells.
Available from: PubMed Central
- "Chitosan-DNA complex and chitosan-plasmid DNA complex are other examples of nanoparticles derived from chitosan-based polyion-complex. The chitosan-plasmid DNA nanoparticles were formulated using complex coacervation and solvent evaporation technique, showing that the release of plasmid DNA from complexes was with a range of 24–96 h depending on the preparation process . "
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ABSTRACT: There has been a great interest in application of nanoparticles as biomaterials for delivery of therapeutic molecules such as drugs and genes, and for tissue engineering. In particular, biopolymers are suitable materials as nanoparticles for clinical application due to their versatile traits, including biocompatibility, biodegradability and low immunogenicity. Biopolymers are polymers that are produced from living organisms, which are classified in three groups: polysaccharides, proteins and nucleic acids. It is important to control particle size, charge, morphology of surface and release rate of loaded molecules to use biopolymer-based nanoparticles as drug/gene delivery carriers. To obtain a nano-carrier for therapeutic purposes, a variety of materials and preparation process has been attempted. This review focuses on fabrication of biocompatible nanoparticles consisting of biopolymers such as protein (silk, collagen, gelatin, β-casein, zein and albumin), protein-mimicked polypeptides and polysaccharides (chitosan, alginate, pullulan, starch and heparin). The effects of the nature of the materials and the fabrication process on the characteristics of the nanoparticles are described. In addition, their application as delivery carriers of therapeutic drugs and genes and biomaterials for tissue engineering are also reviewed.
Available from: Stephan M Ensminger
- "A potential alternative to induce oral tolerance in which the antigen is directly expressed within the intestine could be the use of non-viral gene delivery systems encoding for the antigen. Chitosan, a non-toxic biodegradable polycationic polymer with low immunogenicity, was shown to be a useful oral gene carrier   . Chitosan can be complexed with plasmid- DNA, forming nanoparticles which are stable during the gastrointestinal tract, phagocytized in the gut and causes gene expression. "
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ABSTRACT: One promising approach for the induction of transplant tolerance is the pre-treatment of transplant recipients with donor MHC-alloantigen. Our study focuses on the oral delivery of MHC-antigen encoding genes via chitosan-DNA nanoparticles to modulate the alloimmune response in order to reduce the development of transplant arteriosclerosis, the hallmark feature of chronic rejection after heart transplantation. Therefore, we performed fully allogeneic mouse abdominal aortic transplantats using C57BL/6 (H2(b)) mice as donors and CBA.J (H2(k)) mice as recipients. Aortic grafts were analyzed by histology and morphometry on day 30 after transplantation, levels of circulating alloantibodies were detected by FACS analysis. Pre-treatment of recipient mice with chitosan-DNA nanoparticles encoding for K(b), one of the MHC-I molecules of the donor, resulted in a significant reduction of intimal proliferation compared to untreated controls. When Ovalbumin was fed instead of K(b) encoding nanoparticles (K(b)-NP) or Balb/c (H2(d)) grafts were used instead of C57BL/6 (H2(b)) grafts as antigen controls, both groups showed no reduction of intimal thickness indicating an antigen-specific mechanism. In addition, analysis of peripheral blood of the transplanted mice showed significant suppression of alloantibody formation in the K(b)-NP fed group compared to all other allogeneic transplanted groups suggesting modulation of the humoral immune response. These results demonstrate the potential of chitosan-DNA nanoparticles to induce K(b)-specific tolerance and to reduce the development of transplant arteriosclerosis.
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