Chitosan nanoparticles for siRNA delivery: Optimizing formulation to increase stability and efficiency

Ragelle, Héloïse; Riva, Raphaël; Vandermeulen, Gaëlle; Naeye, Broes; Pourcelle, Vincent; Duff, Cécile S. Le; D'Haese, Cécile; Nysten, Bernard; Braeckmans, Kevin; Smedt, Stefaan C. De; Jérôme, Christine; Préat, Véronique

doi:10.1016/j.jconrel.2013.12.026

Cited by 157 publications

(90 citation statements)

References 41 publications

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“…That is in agreement with previous studies done in different cell line models, i.e. mouse hematopoietic stem cells (Omar Zaki et al, 2015), human respiratory epithelial cells (Grenha et al, 2007), human epithelial liver cells (Yang et al, 2014), mouse epithelial-like cells (Ragelle et al, 2014), mouse fibroblast colon cells (Hallaj-Nezhadi et al, 2011), human mesenchymal stem cells (Corsi et al, 2003) and human embryonic kidney cells (Corsi et al, 2003;Zhou et al, 2015). On the other hand, only a few reports have shown an inhibition in metabolic activity caused by CNs-pDNA treatment (Wimardhani et al, 2014;Yao et al, 2013).…”

Section: Cell Type-dependent Cytostatic Effect Of Cns and Cns-pdnasupporting

confidence: 92%

“…Gene therapy is one of the most promising strategies for treatment of various diseases such as cancer and inflammatory, neurological, cardiovascular or metabolic disorders (Ibraheem et al, 2014;Ragelle et al, 2014). Simultaneously, the choice of a good transfection agent for delivery of nucleic acids is critical for each gene transfer procedure, however most commercially available transfection agents have still some limitations (PerezMartinez et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

“…Among various non-viral vectors, chitosan (CS) is one of the most commonly studied polymer since its positive charges under slightly acidic conditions allow its interaction with nucleic acids and thus formation of complexes of nanoparticles (Ragelle et al, 2014). On the other side, it is known that many biological effects caused by nanoparticles depend on their size, shape, used dose, behavior of nanoparticles in enviroment (i.e., whether or not their aggregation occurs) and cell type (i.e., suspended versus adherent cell types or healthy versus cancer cell types) (Fu et al, 2014;Mytych et al, 2015aMytych et al, , 2015b.…”

Section: Introductionmentioning

confidence: 99%

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Cytotoxic and cytostatic side effects of chitosan nanoparticles as a non-viral gene carrier

Bor

Mytych

Żebrowski

et al. 2016

International Journal of Pharmaceutics

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Section: Cell Type-dependent Cytostatic Effect Of Cns and Cns-pdnasupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Cytotoxic and cytostatic side effects of chitosan nanoparticles as a non-viral gene carrier

Bor

Mytych

Żebrowski

et al. 2016

International Journal of Pharmaceutics

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“…11,12 Various techniques are available to prepare nanoparticles, including solvent evaporation, interfacial polymerization, and emulsion polymerization. 13,14 Unfortunately, these methods frequently require the use of organic solvents or heat, which are undesirable steps and may affect the integrity of components and increase their biological toxicity. 13,15 Among the numerous biological nanomaterials available, chitosan-based nanoparticles are one of the best studied drug delivery systems and have been widely used to load drugs due to the biodegradability and biocompatibility of chitosan.…”

mentioning

confidence: 99%

Novel stable cytokine delivery system in physiological pH solution: chitosan oligosaccharide/heparin nanoparticles

Wang

Tan

Deng

et al. 2015

IJN

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Background Cell therapy is a promising strategy for tissue regeneration. Key to this strategy is mobilization and recruitment of exogenous or autologous stem/progenitor cells by cytokines. However, there is no effective cytokine delivery system available for clinic application, in particular for myocardial regeneration. The aim of this study was to develop a novel cytokine delivery system that is stable in solution at physiological pH. Methods Four groups of self-assembled chitosan oligosaccharide/heparin (CSO/H) nanoparticles were prepared with various volume ratios of chitosan oligosaccharide to heparin (5:2, 5:4, 4:15, 1:5) and characterized by laser diffraction, particle size analysis, and transmission electron microscopy. The encapsulation efficiency and loading content of two cytokines, ie, stromal cell-derived factor (SDF)-1α and vascular endothelial growth factor (VEGF) were quantified using an enzyme-linked immunosorbent assay. The biological activity of the loaded SDF-1α and VEGF was evaluated using the transwell migration assay and MTT assay. The dispersion profiles for the cytokine-loaded nanoparticles were quantified using fluorescence molecular tomography. Results CSO/H nanoparticles were prepared successfully in solution with physiological pH. The particle sizes in the four treatment groups were in the range of 96.2–210.5 nm and the zeta potential ranged from −29.4 mV to 24.2 mV. The loading efficiency in the CSO/H nanoparticle groups with the first three ratios was more than 90%. SDF-1α loaded into CSO/H nanoparticles retained its migration activity and VEGF loaded into CSO/H nanoparticles continued to show proliferation activity. The in vivo dispersion test showed that the CSO/H nanoparticles enabled to VEGF to accumulate locally for a longer period of time. Conclusion CSO/H nanoparticles have a high cytokine loading capacity and allow cytokines to maintain their bioactivity for longer, are stable in an environment with physiological pH, and may be a promising cytokine delivery system for tissue regeneration.

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“…During the past two decades, a substantial amount of work has been published that this polymer is very suitable for preparation of nano-and microparticles for controlled drug release and offers valuable advantages as a drug delivery carrier for both small molecular drugs, like nicotine (Hui Wang, George, Bartlett, Gao, & Islam, 2017), paclitaxel (Majedi et al, 2014), and macromolecules, such as RNA (Ragelle et al, 2014), DNA (Gan, Wang, Cochrane, & McCarron, 2005). A wide range of drug formulations including gels, capsules, tablets, inhalations have been manufactured by CS.…”

Section: Chitosan Nanoparticles As a Pulmonary Delivery Systemmentioning

confidence: 99%

Development of Nicotine Loaded Chitosan Nanoparticles for Lung Delivery

Wang¹

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Cigarette smoking has become one of the leading causes of preventable deaths all over the world, causing a serious threat to human wellbeing and a tremendous economic burden to governments. The currently available treatment options for smoking cessation are not efficient. The pulmonary delivery of drugs by methods such as dry powder inhaler (DPI) has been recognized as one of the most efficient routes of drug delivery to the targeted area. The lung delivery of nicotine in this way would be expected to mimic the effects of tobacco smoking and could significantly reduce the negative health effects of smoking that result from nicotine addiction.The aim of this study is to develop nanoparticles with controlled physicochemical properties using biodegradable polymer of chitosan (CS) loaded with nicotine salt for pulmonary delivery as DPI formulations. The outcomes of this project are expected to be a safe and effective CS-based nicotine formulation for pulmonary delivery to treat nicotine dependence. This thesis specially addresses the research questions: (1) how to develop a feasible process to manufacture the nanoparticles suitable for pulmonary drug delivery using biodegradable polymer of CS containing nicotine salt; (2) how to develop an animal model for pulmonary drug delivery from DPI formulation using a nose-only inhalation device.The current therapeutic options for treatment of smoking addiction have been reviewed, and current advancements of technology in pulmonary drug delivery are summarised. Buccal administration of drugs exhibits a low oral bioavailability, and sublingual tablets and chewing gums can be swallowed before being absorbed.Although nasal spray of nicotine is a fast way to deliver nicotine into the bloodstream, Development of Nicotine Loaded Chitosan Nanoparticles for Lung Delivery iii the rate of absorption is still not as rapid as cigarette smoking. Therefore, it is proposed that delivery of nicotine with sustained drug release profile direct into the deep lung is likely to more effectively mimic the rapid effects of cigarette smoking on a physiological level, which could eliminate patient craving and allow the tapering of nicotine level over time to improve patients' compliance.Water in oil (w/o) emulsion crosslinking method has been used to fabricate nicotine hydrogen tartrate (NHT)-loaded CS nanoparticles which separate as solid microaggregates. The physicochemical properties of particles are characterized by a series of techniques. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) shows that the prepared particles are spherical in morphology with rough surface after loading CS particles with NHT. Dynamic Light Scattering (DLS)by Zetasizer determined nanoparticle size ranging from 167.6 nm to 411 nm, while DLS by Mastersizer demonstrated that the microaggregates of these nanoparticles are in the respirable range (<5µm). The surface positive charge as measured by zeta potential tends to decrease with increase of mass ratios of NHT to CS, which is in contr...

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Chitosan nanoparticles for siRNA delivery: Optimizing formulation to increase stability and efficiency

Cited by 157 publications

References 41 publications

Cytotoxic and cytostatic side effects of chitosan nanoparticles as a non-viral gene carrier

Cytotoxic and cytostatic side effects of chitosan nanoparticles as a non-viral gene carrier

Novel stable cytokine delivery system in physiological pH solution: chitosan oligosaccharide/heparin nanoparticles

Development of Nicotine Loaded Chitosan Nanoparticles for Lung Delivery

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Chitosan nanoparticles for siRNA delivery: Optimizing formulation to increase stability and efficiency

Cited by 157 publications

References 41 publications

Cytotoxic and cytostatic side effects of chitosan nanoparticles as a non-viral gene carrier

Cytotoxic and cytostatic side effects of chitosan nanoparticles as a non-viral gene carrier

Novel stable cytokine delivery system&nbsp;in physiological pH solution: chitosan oligosaccharide/heparin nanoparticles

Development of Nicotine Loaded Chitosan Nanoparticles for Lung Delivery

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Novel stable cytokine delivery system in physiological pH solution: chitosan oligosaccharide/heparin nanoparticles