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- Issa, Mohamed, et al.
(författare)
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Targeted gene delivery with trisaccharide-substituted chitosan oligomers in vitro and after lung administration in vivo
- 2006
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Ingår i: Journal of Controlled Release. - : Elsevier BV. - 0168-3659 .- 1873-4995. ; 115:1, s. 103-112
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to improve the gene delivery efficacy of chitosan oligomer polyplexes by introducing a trisaccharide branch that targets cell-surface lectins. For this purpose, chitosan oligomers were substituted by a trisaccharide with the N-acetylglucosamine residue at the free end, and the ability of the trisaccharide-substituted chitosan oligomers (TCO) polyplexes to transfect various cell lines in vitro and lung tissue after in vivo administration to mice was investigated. Live-cell confocal microscopy showed improved cellular uptake in HEK 293 cells (11-fold, p < 0.001) for the TCO polyplexes compared with the linear chitosan oligomers. Colloidal stability was also enhanced with the substituted form, which suggests that the trisaccharide branch stabilised the polyplexes by means of a steric stabilisation mechanism. Interestingly, gene expression levels in the human liver hepatocyte (HepG2) cells were 10-fold higher with the TCO polyplexes than those mediated by polyethyleneimine. A similar improvement was obtained in a human bronchial epithelial cell line (16HBE14o-). Transfection with the TCO was significantly inhibited (by 30-80%). for all the cell lines tested, in the presence of the free trisaccharide branch, confirming lectin-mediated uptake. Finally, in vivo studies showed that, 24 h after lung administration to mice, luciferase gene expression was 4-fold higher with the TCO than with the corresponding linear chitosan oligomers.
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- Strand, Sabina P, et al.
(författare)
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Tailoring of chitosans for gene delivery : novel self-branched glycosylated chitosan oligomers with improved functional properties
- 2008
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Ingår i: Biomacromolecules. - : American Chemical Society (ACS). - 1526-4602 .- 1525-7797. ; 9:11, s. 3268-76
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Tidskriftsartikel (refereegranskat)abstract
- Chitosan is a promising biomaterial with an attractive safety profile; however, its application potential for gene delivery is hampered by poor compatibility at physiological pH values. Here we have tailored the molecular architecture of chitosan to improve the functional properties and gene transfer efficacy of chitosan oligomers and have developed self-branched glycosylated chitosan oligomer (SB-TCO) substituted with a trisaccharide containing N-acetylglucosamine, AAM. SB-TCO was prepared by controlled depolymerization of chitosan, followed by simultaneous branching and AAM substitution. The product was fully soluble at physiological pH and complexed plasmid DNA into polyplexes of high colloidal and physical stability. SB-TCO displayed high transfection efficacy in HEK293 cells, reaching transfection efficiencies of up to 70%, and large amounts of transgene were produced. Gene transfer efficacy was confirmed in HepG2 cells, where gene expression levels mediated by SB-TCO were up to 10 and 4 times higher than those obtained with unsubstituted and substituted linear oligomers, respectively. The rapid onset of transgene expression in both cell lines indicates efficient DNA release and transcription from SB-TCO polyplexes. In comparison with 22 kDa linear PEI-based transfection reagent used as the control, SB-TCO possessed higher gene transfer efficacy, significantly lower cytotoxicity, and improved serum compatibility.
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- Söderström, J., et al.
(författare)
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X-ray yield and selectively excited X-ray emission spectra of atenolol and nadolol
- 2005
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Ingår i: Journal of Electron Spectroscopy and Related Phenomena. - : Elsevier BV. - 0368-2048 .- 1873-2526. ; 144, s. 283-285
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Tidskriftsartikel (refereegranskat)abstract
- A pre-study in a project aimed at increasing the understanding of drug solubility by applying X-ray spectroscopy to substances in solid phases, in aqueous solution, and in gas-phase is presented. Influence of the molecular surrounding on the local electronic structure is reflected in X-ray yield fine structure, and in site-selectively excited X-ray emission spectra. Results for atenolol and nadolol in solid form are discussed.
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