Advanced nanogel engineering for drug delivery

Raemdonck, Koen; Demeester, Joseph; Smedt, Stefaan De

doi:10.1039/b811923f

Cited by 451 publications

(300 citation statements)

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“…During the last decade, an increasing number of publications describes nanoscopic hydrogels as drug delivery carriers, though only a few reports are available on nanogels for siRNA delivery [21]. In this report, cationic dextran nanogels loaded with siRNA are studied [22].…”

Section: Introductionmentioning

confidence: 99%

Prolonged gene silencing by combining siRNA nanogels and photochemical internalization

Raemdonck

Naeye

Høgset

et al. 2010

Journal of Controlled Release

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Small interfering RNAs (siRNAs) show potential for the treatment of a wide variety of pathologies with a known genetic origin through sequence-specific gene silencing. However, siRNAs do not have favorable drug-like properties and need to be packaged into nanoscopic carriers that are designed to guide the siRNA to the cytoplasm of the target cell. In this report biodegradable cationic dextran nanogels are used to deliver siRNA across the intracellular barriers. For the majority of non-viral siRNA carriers studied so far, endosomal confinement is identified as the most prominent hurdle, limiting the full gene silencing potential. Thus, there is a major interest in methods that are able to enhance endosomal escape of siRNA to improve its intracellular bioavailability. Photochemical internalization (PCI) is a method that employs amphiphilic photosensitizers to destabilize endosomal vesicles. We show that applying PCI at a later time-point post-transfection significantly prolonged the knockdown of the target protein only in case the siRNA was carried by nanogels and not when a liposomal carrier was used. Combining siRNA nanogels and PCI creates new possibilities to prolong gene silencing by using intracellular vesicles as depots for siRNA and applying PCI at the time when maintaining the RNAi effect becomes critical. Graphical abstractCombining siRNA nanogels and photochemical internalization (PCI) creates new possibilities to prolong gene silencing by using intracellular vesicles as depots and applying PCI at the time when maintaining the RNAi effect becomes critical.

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Section: Introductionmentioning

confidence: 99%

Prolonged gene silencing by combining siRNA nanogels and photochemical internalization

Raemdonck

Naeye

Høgset

et al. 2010

Journal of Controlled Release

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“…Although such dex-HEMA nanogels are also ideally sized for intravenous delivery to tumors (approximately 180 nm), they likely possess insufficient circulation times to enable an adequate extravasation and accumulation in the tumor tissue (Raemdonck et al, 2009a, Raemdonck et al, 2009b. As discussed above, PEGylation of these nanogels should not only improve their circulation time but also minimize their aggregation following intravenous injection.…”

Section: Introductionmentioning

confidence: 99%

PEGylation of biodegradable dextran nanogels for siRNA delivery

Naeye

Raemdonck

Remaut

et al. 2010

European Journal of Pharmaceutical Sciences

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In this paper we report on various ways to PEGylate dextran nanogels. PEGylation could be a valuable asset for the application of dextran nanogels in vivo as this will probably result in an improved pharmacokinetic profile of these carriers. We have shown that covalent coupling of PEG to nanogels is possible and that this approach is most suited compared to other methods of PEGylation.We hope that our manuscript will be of interest to your readership,

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“…An important distinction from numerous other delivery systems is that the active compound is structurally not a part of the matrix itself. Many of these matrices are designated as hydrogels, which are by definition hydrophilic polymeric networks with a three-dimensional configuration capable of imbibing high amounts of water or biological fluids [34][35][36][37]. However, some important and highly investigated matrix systems, i.e.…”

Section: Introductionmentioning

confidence: 99%

Hemocompatibility of siRNA loaded dextran nanogels

et al. 2011

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Over the last decade, considerable effort has been put in the implementation of RNA interference (RNAi) as a treatment for various disorders. As RNAi occurs in the cytoplasm of cells, it is imperative that RNAi mediators such as small interfering RNA (siRNA) cross several extracellular and intracellular barriers to reach this site of action. Among the extensive range of proposed delivery systems for siRNA, matrix systems possess interesting properties to promote the delivery of siRNA to a target tissue. In this review, a number of recently developed matrix and hybrid systems for siRNA delivery are discussed.

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Advanced nanogel engineering for drug delivery

Cited by 451 publications

References 100 publications

Prolonged gene silencing by combining siRNA nanogels and photochemical internalization

Prolonged gene silencing by combining siRNA nanogels and photochemical internalization

PEGylation of biodegradable dextran nanogels for siRNA delivery

Hemocompatibility of siRNA loaded dextran nanogels

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