Dual crosslinked hydrogel nanoparticles by nanogel bottom-up method for sustained-release delivery

Shimoda, Asako; Sawada, Sumiyuki; Kano, Arihiro; Maruyama, Atsushi; Moquin, Alexandre; Winnik, Françoise M.; Akiyoshi, Kazunari

doi:10.1016/j.colsurfb.2011.09.025

Cited by 65 publications

(50 citation statements)

References 29 publications

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“…18 Nuclear magnetic resonance characterization of the CHPOA nanogels and NanoClik nanoparticles has been described previously. 18 CHPOA nanogels were suspended in phosphate-buffered saline at 10 mg/mL. The suspension was mixed with a solution of W9 and kept overnight at 4°C to form the CHPOA-W9 complex.…”

Section: Methodsmentioning

confidence: 99%

“…15,16 However, CHP nanogels rapidly release the proteins incorporated in the complex in the bloodstream following displacement of the protein by serum proteins, 17 presumably because CHP nanogels are crosslinked exclusively by physical forces, without any covalent interactions. 17,18 Modification of molecules by polyethylene glycol (PEG) is often performed to enhance drug retention, [19][20][21] and this PEGylation has been proven to induce favorable pharmacokinetics and to reduce the toxicity and immunogenicity of drugs. 22 Injectable nanocarriers (NanoClik nanoparticles) 10 where the acryloyl group has been modified in cholesterol-bearing pullulan (CHPOA) nanogels crosslinked by pentaerythritol tetra (mercaptoethyl) polyoxyethylene (PEGSH) have been synthesized to overcome the rapid release of the incorporated protein from the CHP nanogels.…”

mentioning

confidence: 99%

“…22 Injectable nanocarriers (NanoClik nanoparticles) 10 where the acryloyl group has been modified in cholesterol-bearing pullulan (CHPOA) nanogels crosslinked by pentaerythritol tetra (mercaptoethyl) polyoxyethylene (PEGSH) have been synthesized to overcome the rapid release of the incorporated protein from the CHP nanogels. 18,23 Transmission electron microscopy images of NanoClik nanoparticles showed that the nanogels were gathered together to form one particle, which was a raspberrylike structure. 18 The chemical crosslinking of nanogels with PEG derivatives has allowed for prevention of non-specific protein adsorption, 18,24,25 thereby slowing the exchange rate of an incorporated protein with serum proteins.…”

mentioning

confidence: 99%

“…18,23 Transmission electron microscopy images of NanoClik nanoparticles showed that the nanogels were gathered together to form one particle, which was a raspberrylike structure. 18 The chemical crosslinking of nanogels with PEG derivatives has allowed for prevention of non-specific protein adsorption, 18,24,25 thereby slowing the exchange rate of an incorporated protein with serum proteins. Furthermore, the NanoClik nanoparticles also provide higher structural stability when compared with conventional CHP nanogels.…”

mentioning

confidence: 99%

“…Furthermore, the NanoClik nanoparticles also provide higher structural stability when compared with conventional CHP nanogels. 18 The W9 peptide is an inhibitor of osteoclast formation that acts by antagonizing the effects of the receptor activator of nuclear factor kappa B ligand (RANKL), a critical molecule required for osteoclastogenesis. 26,27 W9 efficiently prevented bone loss by inhibiting osteoclast formation in murine bone resorption models in vivo, including a low calcium diet model.…”

mentioning

confidence: 99%

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Nanogel-crosslinked nanoparticles increase the inhibitory effects of W9 synthetic peptide on bone loss in a murine bone resorption model

Sato¹,

Alles²,

Khan³

et al. 2015

IJN

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We investigated the biological activity of W9, a bone resorption inhibitor peptide, using NanoClik nanoparticles as an injectable carrier, where acryloyl group-modified cholesterol-bearing pullulan (CHPOA) nanogels were crosslinked by pentaerythritol tetra (mercaptoethyl) polyoxyethylene. Thirty 5-week-old male C57BL/6J mice were fed a low calcium diet and received once-daily subcutaneous injections of the carrier alone, W9 24 mg/kg/day alone, W9 24 mg/kg/day incorporated in cholesterol bearing pullulan (CHP) nanogels, or W9 (8 and 24 mg/kg/day) incorporated in NanoClik nanoparticles for 4 days (n=5). Mice that received a normal calcium diet with NanoClik nanoparticle injections without W9 were used as a control group. Radiological analyses showed that administration of W9 24 mg/kg/day significantly prevented low calcium-induced reduction of bone mineral density in the long bones and lumbar vertebrae, but only when the NanoClik nanoparticles were used as a carrier. Histomorphometric analyses of the proximal tibiae revealed that W9 24 mg/kg/day incorporated in NanoClik nanoparticles prevented the increase in bone resorption indices induced by a low calcium diet, which was confirmed by measurement of serum bone resorption markers. These data suggest that NanoClik nanoparticles could be a useful carrier for peptide therapeutics, and also demonstrate that daily subcutaneous injections of the W9 peptide with the nanoparticles were able to inhibit bone loss in vivo. An osteoclastogenesis inhibition assay performed in vitro confirmed a slower release profile of W9 from NanoClik nanoparticles compared with conventional CHP nanogels.

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Section: Methodsmentioning

confidence: 99%