Degradation Kinetics of Methacrylated Dextrans in Aqueous Solution

Dijk-Wolthuis, W. N. E. Van; Steenbergen, M.J. van; Underberg, W.J.M.; Hennink, W.E.

doi:10.1021/js9604220

Cited by 99 publications

(104 citation statements)

References 11 publications

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“…At this moment we do not have conclusive data on the degradation of the DS 5.2 nanogels in the endolysosomal compartment. Early data in the literature [28] state that hydrolysis of the dex-HEMA carbonate ester is minimal at the acidic pH found in endolysosomes (pH ~4.5-5) and as a consequence the nanogel degradation will be substantially slower than at neutral pH. It still remains to be evaluated if after 6 days siRNA nanogels or decomplexed (free) siRNA is released into the cytoplasm.…”

Section: Resultsmentioning

confidence: 99%

“…To prepare cationic nanogels dex-(HE)MA is copolymerized with TMAEMA (and/or AEMA) by a mini-emulsion photopolymerization (see Supplementary Information) [22,27]. While dex-HEMA based nanogels are biodegradable (through hydrolysis of the carbonate ester) dex-MA based nanogels are not as it does not contain a labile ester bond between the methacrylate moiety and the dextran backbone [22,27,28]. Nanogels are loaded with siRNA by rehydrating a weighed amount of nanogel lyophilizate with HEPES buffer and mixing the resulting dispersion with an equal volume of siRNA solution.…”

Section: Figmentioning

confidence: 99%

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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: Resultsmentioning

confidence: 99%

Section: Figmentioning

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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“…However, most of these hydrogels are not biodegradable and therefore, limiting the clinical use in vivo when implanted. There have been several attempts to prepare a wide range of biodegradable hydrogels by incorporating chemically hydrolyzable or biochemically cleavable groups into the polymer network structure 5,6) . Aliphatic polyesters such as poly(L-lactide) (PLLA) and its copolymers with glycolic acid have been known as representative biodegradable polymers because of their proven biocompatibility and versatile degradation properties.…”

Section: Introductionmentioning

confidence: 99%

A new class of biodegradable hydrogels stereocomplexed by enantiomeric oligo(lactide) side chains of poly(HEMA‐ g ‐OLA)s

Lim

Choi

Park³

2000

Macromol. Rapid Commun.

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Two enantiomeric amphiphilic graft copolymers consisting of water soluble poly(2‐hydroxyethyl methacrylate) (HEMA) and biodegradable oligo(L‐lactide) (OLLA) or oligo(D‐lactide) (ODLA) were synthesized by free radical copolymerization. HEMA‐OL(D)LA macromonomers were synthesized by ring opening polymerization of L‐ or D‐lactide. Both HEMA‐OLA macromonomers and graft copolymers were characterized by NMR spectroscopy and gel permeation chromatography. Graft copolymers and their stereocomplexes were analyzed by wide angle X‐ray diffraction and differential scanning calorimetry (DSC). Due to the formation of stereocomplex crosslinks between poly(HEMA) main chains, amphiphilic, biodegradable hydrogels prepared by blending of two enantiomeric poly(HEMA‐g‐OLLA) and poly(HEMA‐g‐ODLA) degraded more slowly in phosphate buffered saline than individual optically pure poly‐(HEMA‐g‐OL(D)LA).

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“…DMAEMA oligomers are generated as degradation products, [28,30,31] which increase the inner (osmotic) pressure in the LbL coated gel beads. Figure 3 shows the behavior of the LbL coated gel beads containing (A) nondissolved and (B) dissolved CaCO 3 cores upon adding NaOH.…”

mentioning

confidence: 99%

Self‐Exploding Beads Releasing Microcarriers

et al. 2008

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Although significant progress in the vaccine delivery has been made during the last decades, there remain many major challenges for optimal delivery of vaccines. [1,2] Two unmet needs are (i) the administration of prime and booster doses (required to generate sufficient immunity) by a single injection and (ii) the co-delivery of the adjuvant and the antigen to antigen presenting cells (APC) to enhance or bias the immune response. Enhanced antigen presentation and better immune responses have been reported in case the antigen is encapsulated in microparticles which are phagocytosed by dendritic cells. [3][4][5][6] By encapsulating antigen in microparticles they are due to their size more targeted to APC's, leading to an increased antigen uptake and a 100-to 1000-fold increase in antigen presentation by both MHC I and MHC II class molecules. It would thus be an enormous benefit if scientists could develop an injection that after a single shot delivers (a) multiple doses (thus avoiding the multiple injections which are currently needed) of (b) antigen and adjuvant containing microparticles to APC's. Previously we introduced self-exploding microcapsules, 5-15 mm in size, which consisted of a degradable hydrophilic microgel core surrounded by a semi-permeable polyelectrolyte membrane. [7][8][9][10] Upon dispersing such microcapsules in an aqueous environment water entered the microcapsules and hydrolyzed the crosslinks of the microgel. This resulted in the swelling of the microgel core which at a certain moment ruptured the polyelectrolyte membrane thereby suddenly releasing FITC-dextran which was encapsulated in the microgel core. As schematically illustrated in Figure 1A, in this Communication we design self-exploding polyelectrolyte coated gel beads releasing micrometer-sized capsules at the time of explosion. The gel beads have a mean diameter of 150 mm and are loaded with 3 mm sized layer-by-layer (LbL) microcapsules. The LbL microcapsules [11][12][13][14][15] are fabricated by sequential adsorption of (bio)polyanions and (bio)polycations (named LbL [16] coating) onto a spherical template followed by the decomposition of this template. We show that when the polyelectrolyte coated gel beads explode the smaller LbL microcapsules become suddenly released. We and others have reported before that LbL microcapsules (1) can encapsulate high amounts of proteins in an intact state, [17][18][19][20] and (2) are taken up and degraded by dendritic cells, both in vitro as well as in vivo. [21,22] In view of this, we reasoned that self-exploding gel beads releasing antigen containing LbL microcapsules at different times after injection could become promising materials for vaccination purposes. The specific aim of this paper is two-fold. First, we aim to show that a polyelectrolyte coated spherical gel bead can be loaded with LbL microcapsules.Next we aim to demonstrate the sudden release of these LbL microcapsules upon the rupturing of the polyelectrolyte shell on the surface of the gel beads. Calcium carbonate (CaCO 3 ) core ...

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Degradation Kinetics of Methacrylated Dextrans in Aqueous Solution

Cited by 99 publications

References 11 publications

Prolonged gene silencing by combining siRNA nanogels and photochemical internalization

Prolonged gene silencing by combining siRNA nanogels and photochemical internalization

A new class of biodegradable hydrogels stereocomplexed by enantiomeric oligo(lactide) side chains of poly(HEMA‐ g ‐OLA)s

Self‐Exploding Beads Releasing Microcarriers

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