A novel chitosan oligosaccharide–stearic acid micelles for gene delivery: Properties and in vitro transfection studies

Hu, Fuqiang; Zhao, Miaomiao; Yuan, Hong; You, Jian; Du, Yong‐Zhong; Zeng, Su

doi:10.1016/j.ijpharm.2006.02.026

Cited by 192 publications

(139 citation statements)

References 34 publications

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“…The data did not show evidence of cytotoxicity after 4 h of incubation with the systems based on chitosan. Similar studies using chitosan (Santos-Carballal et al, 2015) and chitosan derivatives (Hu et al, 2006) in comparison with Lipofectamine-based systems are found in the literature, where chitosan did not exhibit cytotoxic effects and…”

Section: Discussionsupporting

confidence: 85%

Chitosan as a non-viral co-transfection system in a cystic fibrosis cell line

Fernández

Santos-Carballal

Weber

et al. 2016

International Journal of Pharmaceutics

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Successful gene therapy requires the development of suitable vehicles for the selective and efficient delivery of genes to specific target cells at the expense of minimal toxicity. In this work, we investigated a non-viral gene delivery system based on chitosan (CS) to specifically address cystic fibrosis (CF). Thus, electrostatic self-assembled CS-pEGFP and CS-pEGFPsiRNA complexes were prepared from high-pure fully characterized CS (Mw ~20 kDa and degree of acetylation ~30%). The average diameter of positively-charged complexes (i.e.  ~ +25 mV) was ~200 nm. The complexes were found relatively stable over 14 h in OptiMEM. Cell viability study did not show any significant cytotoxic effect of the CS-based complexes in a human bronchial cystic fibrosis cell line (s). We evaluated the transfection efficiency of this cell line with both CS-pEGFP and co-transfected with CS-pEGFP-siRNA complexes at (N/P) charge ratio of 12. We reported an increase in the fluorescence intensity of CS-pEGFP and a reduction in the cells co-transfected with CS-pEGFP-siRNA. This study shows proof-of-principle that co-transfection with chitosan might be an effective delivery system in a human CF cell line. It also offers a potential alternative to further develop therapeutic strategies for inherited disease treatments, such as CF.

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Section: Discussionsupporting

confidence: 85%

Chitosan as a non-viral co-transfection system in a cystic fibrosis cell line

Fernández

Santos-Carballal

Weber

et al. 2016

International Journal of Pharmaceutics

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“…16 Studies have shown that CS can transiently open tight junctions, resulting in a paracellular pathway of material through the epithelial barrier. 17 In our previous studies, stearic acid-grafted CS (CS-SA) was synthesized using low molecular-weight CS, which was able to form micelle-like nanoparticles in the aqueous phase, and has been used to deliver gene 18 and antitumor agents like doxorubicin 19,20 and paclitaxel. 21 All the results demonstrated the excellent biomembrane penetration ability of CS-SA, indicated by rapid in vitro cellular uptake and comparable in vivo therapeutic effect with a commercial agent.…”

Section: Introductionmentioning

confidence: 99%

“…Stearic acid (SA) was conjugated onto CS with 18-KDa weight average molecular weight using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC)as the coupling reagent. 18,19 The physicochemical characteristics of CS-SA were then investigated. In vitro cellular uptake and cytotoxicity were performed on bEnd.3 cells.…”

Section: Introductionmentioning

confidence: 99%

Brain-targeting study of stearic acid–grafted chitosan micelle drug-delivery system

Xie¹,

Du²,

Yuan³

et al. 2012

IJN

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Purpose: Therapy for central nervous system disease is mainly restricted by the blood-brain barrier. A drug-delivery system is an effective approach to overcome this barrier. In this research, the potential of polymeric micelles for brain-targeting drug delivery was studied. Methods: Stearic acid-grafted chitosan (CS-SA) was synthesized by hydrophobic modification of chitosan with stearic acid. The physicochemical characteristics of CS-SA micelles were investigated. bEnd.3 cells were chosen as model cells to evaluate the internalization ability and cytotoxicity of CS-SA micelles in vitro. Doxorubicin (DOX), as a model drug, was physically encapsulated in CS-SA micelles. The in vivo brain-targeting ability of CS-SA micelles was qualitatively and quantitatively studied by in vivo imaging and high-performance liquid chromatography analysis, respectively. The therapeutic effect of DOX-loaded micelles in vitro was performed on glioma C6 cells. Results:The critical micelle concentration of CS-SA micelles with 26.9% ± 1.08% amino substitute degree was 65 µg/mL. The diameter and surface potential of synthesized CS-SA micelles in aqueous solution was 22 ± 0.98 nm and 36.4 ± 0.71 mV, respectively. CS-SA micelles presented excellent cellular uptake ability on bEnd.3 cells, the IC 50 of which was 237.6 ± 6.61 µg/mL. DOX-loaded micelles exhibited slow drug-release behavior, with a cumulative release up to 72% within 48 hours in vitro. The cytotoxicity of DOX-loaded CS-SA micelles against C6 was 2.664 ± 0.036 µg/mL, compared with 0.181 ± 0.066 µg/mL of DOX ⋅ HCl. In vivo imaging results indicated that CS-SA was able to transport rapidly across the blood-brain barrier and into the brain. A maximum DOX distribution in brain of 1.01%/g was observed 15 minutes after administration and maintained above 0.45%/g within 1 hour. Meanwhile, free DOX ⋅ HCl was not detected in brain. In other major tissues, DOX-loaded micelles were mainly distributed into lung, liver, and spleen, with a reduction of DOX accumulation in heart. Conclusion: The CS-SA micelles were able to be used as a promising carrier for a braintargeting drug delivery system.

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“…25 Stearic acid was obtained from Chemical Reagent Co Ltd (Shanghai, China). 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC), 2,4,6-trinitrobenzene sulfonic acid (TNBS), and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) were purchased from Sigma (St Louis, MO).…”

Section: Materials and Methods Materialsmentioning

confidence: 99%

Receptor-mediated gene delivery by folic acid-modified stearic acid-grafted chitosan micelles

Du¹,

Cai²,

Li³

et al. 2011

IJN

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Background Cationic polymers have been accepted as effective nonviral vectors for gene delivery with low immunogenicity unlike viral vectors. However, the lack of organ or cell specificity sometimes hampers their application and the modification of polymeric vectors has also shown successful improvements in achieving cell-specific targeting delivery and in promoting intracellular gene transfer efficiency. Methods A folic acid-conjugated stearic acid-grafted chitosan (FA-CS-SA) micelle, synthesized by a 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide-coupling reaction, was designed for specific receptor-mediated gene delivery. Results Due to the cationic properties of chitosan, the micelles could compact the plasmid DNA (pDNA) to form micelle/pDNA complexes nanoparticles. The particle size and zeta potential of the FA-CS-SA/pDNA complexes with different N/P ratios were 100–200 nm and −20 to −10 mV, respectively. The DNase I protection assay indicated that the complexes can efficiently protect condensed DNA from enzymatic degradation by DNase I. A cytotoxicity study indicated that the micelles exhibited less toxicity in comparison with Lipofectamine TM 2000. Using SKOV3 and A549 as model tumor cells, the cellular uptake of micelles was investigated. Conclusion It was found that cellular uptake of FA-CS-SA in SKOV3 cells with higher folate receptor expression was faster than that in A549 cells with a short incubation time. Luciferase assay and green fluorescent protein detection were used to confirm that FA-CS-SA could be an effective gene vector. Transfection efficiency of the FA-CS-SA/pDNA complexes in SKOV3 cells was enhanced up to 2.3-fold compared with that of the CS-SA/pDNA complexes. However, there was no significant difference between the transfection efficiencies of the two complexes in A549 cells. Importantly, the transfection efficiency of FA-CS-SA/pDNA decreased with free FA pretreatment in SKOV3 cells. It was concluded that the increase in transfection efficiency of the FA-CS-SA/pDNA complexes was attributed to folate receptor-mediated endocytosis.

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A novel chitosan oligosaccharide–stearic acid micelles for gene delivery: Properties and in vitro transfection studies

Cited by 192 publications

References 34 publications

Chitosan as a non-viral co-transfection system in a cystic fibrosis cell line

Chitosan as a non-viral co-transfection system in a cystic fibrosis cell line

Brain-targeting study of stearic acid–grafted chitosan micelle drug-delivery system

Receptor-mediated gene delivery by folic acid-modified stearic acid-grafted chitosan micelles

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A novel chitosan oligosaccharide–stearic acid micelles for gene delivery: Properties and in vitro transfection studies

Cited by 192 publications

References 34 publications

Chitosan as a non-viral co-transfection system in a cystic fibrosis cell line

Chitosan as a non-viral co-transfection system in a cystic fibrosis cell line

Brain-targeting study of stearic acid&ndash;grafted chitosan micelle drug-delivery system

Receptor-mediated gene delivery by folic acid-modified stearic acid-grafted chitosan micelles

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Brain-targeting study of stearic acid–grafted chitosan micelle drug-delivery system