Bioadhesive hyaluronan–chitosan nanoparticles can transport genes across the ocular mucosa and transfect ocular tissue

Fuente, María de la; Seijo, Begoña; Alonso, Marı́a José

doi:10.1038/gt.2008.16

Cited by 175 publications

(103 citation statements)

References 41 publications

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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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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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“…O potencial zeta das soluções coletadas aumentou com o valor de RGlyCHI/TPP, como era esperado pelo aumento das cargas positivas provenientes dos grupos amino da GlyCHI (Lee et al, 2004), porém apresentou-se negativo ou muito próximo de zero. Esse fator pode limitar a aplicabilidade biológica das nanopartículas produzidas, pois, além de não apresentarem estabilidade coloidal, os valores positivos de potencial zeta seriam desejáveis para aplicações de gene delivery, considerando a interação entre os vetores não virais catiônicos e a membrana celular negativa (la Fuente, de et al, 2008).…”

Section: Ufscar -São Carlos -Sp 16 a 19 De Julho De 2017unclassified

Sistema Microfluídico Para Produção De Nanopartículas De Quitosana Glicosilada E Tripolifosfato De Sódio

Mustafa¹,

Pessoa²,

Perli³

et al. 2017

Blucher Chemical Engineering Proceedings

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“…86 Nanopartículas híbridas de quitosana com ácido hialurônico foram capazes de transfectar in vitro células HCE e IOBA-NHC, utilizando diferentes modelos de pDNA como pEGFP (proteína verde fluorescente), pSEAP (fosfatase alcalina) e pLac-Z (β-galactosidase). 87,88 O grau de polimerização (i.e. peso molecular) parece influenciar na transfecção, sendo oligômeros (<10-12 kDa) mais eficazes em transfectar células de córnea HCE.…”

Section: Polímeros Catiônicos Quitosanaunclassified

Biomateriais para formulações de base nanotecnológica visando terapia gênica ocular

et al. 2016

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Bioadhesive hyaluronan–chitosan nanoparticles can transport genes across the ocular mucosa and transfect ocular tissue

Cited by 175 publications

References 41 publications

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

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

Sistema Microfluídico Para Produção De Nanopartículas De Quitosana Glicosilada E Tripolifosfato De Sódio

Biomateriais para formulações de base nanotecnológica visando terapia gênica ocular

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