Targeted gene delivery with trisaccharide-substituted chitosan oligomers in vitro and after lung administration in vivo

Issa, Mohamed; Köping-Höggård, Magnus; Tømmeraas, Kristoffer; Vårum, Kjell M.; Christensen, Bjørn E.; Strand, Sabina P.; Artursson, Per

doi:10.1016/j.jconrel.2006.06.029

Cited by 84 publications

(64 citation statements)

References 37 publications

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“…The chemical structures of polymers for polymeric nanoparticles used in pulmonary delivery systems are shown Figure 2. 26,29,38,39,[54][55][56][57]59,61,69,70,74,75,[79][80][81][82][83][84][85][86][87][88][89][90][91][92][93] Due to their biocompatibility, surface modification capability, and sustained-release properties, polymeric nanoparticles are intensively studied using various important pulmonary drugs. These pulmonary drug include antiasthmatic drugs, 22,26 antituberculosis drugs, 38,39 pulmonary hypertension drugs, 29 and anticancer drugs.…”

Section: Drugs For Inhalationmentioning

confidence: 99%

Nanomedicine in pulmonary delivery

Mansour¹,

Rhee²,

Wu³

2009

IJN

409

269

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Section: Drugs For Inhalationmentioning

confidence: 99%

Nanomedicine in pulmonary delivery

Mansour¹,

Rhee²,

Wu³

2009

IJN

409

269

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“…Other in vivo studies report appreciable protein expression using chitosan as condensing carrier for plasmid delivery. Chitosans with various MW and DDA have been successfully used for systemic, 26 IM, 27 intratracheal, [28][29][30] oral, 31 topical, 32 and direct intestinal 15 administration of plasmid DNA. In most of these studies, reporter genes such as luciferase or EGFP were used.…”

Section: Introductionmentioning

confidence: 99%

Chitosan–plasmid nanoparticle formulations for IM and SC delivery of recombinant FGF-2 and PDGF-BB or generation of antibodies

et al. 2009

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Growth factor therapy is an emerging treatment modality that enhances tissue vascularization, promotes healing and regeneration and can treat a variety of inflammatory diseases. Both recombinant human growth factor proteins and their gene therapy are in human clinical trials to heal chronic wounds. As platelet-derived growth factor-bb (PDGF-BB) and fibroblast growth factor-2 (FGF-2) are known to induce chemotaxis, proliferation, differentiation, and matrix synthesis, we investigated a non-viral means for gene delivery of these factors using the cationic polysaccharide chitosan. Chitosan is a polymer of glucosamine and N-acetylglucosamine, in which the percentage of the residues that are glucosamine is called the degree of deacetylation (DDA). The purpose of this study was to express PDGF-BB and FGF-2 genes in mice using chitosan-plasmid DNA nanoparticles for the controlled delivery of genetic material in a specific, efficient, and safe manner. PDGF-BB and FGF-2 genes were amplified from human tissues by RT-PCR. To increase the secretion of FGF-2, a recombinant 4sFGF-2 was constructed bearing eight amino-acid residues of the signal peptide of FGF-4. PCR products were inserted into the expression vector pVax1 to produce recombinant plasmids pVax1-4sFGF2 and pVax1-PDGF-BB, which were then injected into BALB/C mice in the format of polyelectrolyte nanocomplexes with specific chitosans of controlled DDA and molecular weight, including 92-10, 80-10, and 80-80 (DDA-number average molecular weight or M n in kDa). ELISA assays on mice sera showed that recombinant FGF-2 and PDGF-BB proteins were efficiently expressed and specific antibodies to these proteins could be identified in sera of injected mice, but with levels that were clearly dependent on the specific chitosan used. We found high DDA low molecular weight chitosans to be efficient protein expressors with minimal or no generation of neutralizing antibodies, while lowering DDA resulted in greater antibody levels and correspondingly lower levels of detected recombinant protein. Histological analyses corroborated these results by revealing greater inflammatory infiltrates in lower DDA chitosans, which produced higher antibody titers. We found, in general, a more efficient delivery of the plasmids by subcutaneous than by intramuscular injection. Specific chitosan carriers were identified to be either efficient non-toxic therapeutic protein delivery systems or vectors for DNA vaccines.

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“…In order to improve the stability and increase the circulation lifetime of the polyplexes, PEGylation [50], quaternization [51] and glycolyzation [52] of the polymer have been proposed.…”

Section: Colloidal Stability In Physiological Conditionsmentioning

confidence: 99%

“…Moreover, grafting Ch with arginine has been proven to increase cell uptake and PEG-succinimidyl ester or Folate-PEG-COOH molecules could enhance pharmacokinetics [76] Finally, the reductive N-alkylation method serves to graft an aldehyde derivative on the amine of Ch. Grafted species include fluorescent probes as 9-anthraldehyde [77], phosphorylcholine [78,79], oligosaccharides [18,46,52,80] and dextran like polymers [81]. Normally, reductive N-alkylation is directed to reduce cytotoxicity and increase transfection efficiency.…”

Section: Chemical Modifications Of Ch To Overcome Transfection Barriersmentioning

confidence: 99%

“…This occurs as a result of the weaker association of pDNA to Ch and the retained capacity of the polymer to protect the plasmid against DNase degradation, enabling an efficient release and delivery of the intact transgene [22]. Trisaccharide-sustituted Ch oligomers have been also administered via the trachea, observing luciferase gene expression in the mouse lung 24 hours post administration [52].…”

Section: Lung Deliverymentioning

confidence: 99%

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Low Molecular Weight Chitosan (LMWC)-based Polyplexes for pDNA Delivery: From Bench to Bedside

et al. 2014

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Non-viral gene delivery vectors are emerging as a safer alternative to viral vectors. Among natural polymers, chitosan (Ch) is the most studied one, and low molecular weight Ch, specifically, presents a wide range of advantages for non-viral pDNA delivery. It is crucial to determine the best process for the formation of Low Molecular Weight Chitosan (LMWC)-pDNA complexes and to characterize their physicochemical properties to better understand their behavior once the polyplexes are administered. The transfection efficiency of Ch based polyplexes is relatively low. Therefore, it is essential to understand all the transfection process, including the cellular uptake, endosomal escape and nuclear import, together with the parameters involved in the process to improve the design and development of the non-viral vectors. The aim of this review is to describe the formation and characterization of LMWC based polyplexes, the in vitro transfection process and finally, the in vivo applications of LMWC based polyplexes for gene therapy purposes.

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Targeted gene delivery with trisaccharide-substituted chitosan oligomers in vitro and after lung administration in vivo

Cited by 84 publications

References 37 publications

Nanomedicine in pulmonary delivery

Nanomedicine in pulmonary delivery

Chitosan–plasmid nanoparticle formulations for IM and SC delivery of recombinant FGF-2 and PDGF-BB or generation of antibodies

Low Molecular Weight Chitosan (LMWC)-based Polyplexes for pDNA Delivery: From Bench to Bedside

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