Raspberry-like assembly of cross-linked nanogels for protein delivery

Urara Hasegawa; Shin ichi Sawada; Takeshi Shimizu; Tsunao Kishida; Eigo Otsuji; Osam Mazda; Kazunari Akiyoshi

doi:10.1016/j.jconrel.2009.06.025

Raspberry-like assembly of cross-linked nanogels for protein delivery

Urara Hasegawa
, Shin ichi Sawada
, Takeshi Shimizu
, Tsunao Kishida
, Eigo Otsuji
, Osam Mazda
, Kazunari Akiyoshi

Materials Science and Engineering

Research output: Contribution to journal › Article › peer-review

117 Scopus citations

Abstract

Raspberry-like assembly of nanogels (A-CHPNG) with a high potential as a carrier for protein delivery was prepared. Cross-linking of acrylate group-modified cholesterol-bearing pullulan nanogel (CHPANG) with thiol group-modified poly (ethylene glycol) (PEGSH) by Michael addition yielded A-CHPNG with narrow size distribution. The size of A-CHPNGs was controlled in the range of 40-120 nm by changing the concentration of CHPANG and PEGSH. A-CHPNG gradually degraded by hydrolysis under physiological condition and seemed to dissociate back to original nanogel. A-CHPNG encapsulated interleukin-12 (IL-12) efficiently (96%) and stably kept it in the presence of BSA (50 mg/ml). In addition, A-CHPNG had a high potential to maintain a high IL-12 level in plasma after subcutaneous injection in mice. Therefore, A-CHPNG is a promising carrier for long-term medications.

Original language	English (US)
Pages (from-to)	312-317
Number of pages	6
Journal	Journal of Controlled Release
Volume	140
Issue number	3
DOIs	https://doi.org/10.1016/j.jconrel.2009.06.025
State	Published - Dec 16 2009

All Science Journal Classification (ASJC) codes

Pharmaceutical Science

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10.1016/j.jconrel.2009.06.025

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title = "Raspberry-like assembly of cross-linked nanogels for protein delivery",

abstract = "Raspberry-like assembly of nanogels (A-CHPNG) with a high potential as a carrier for protein delivery was prepared. Cross-linking of acrylate group-modified cholesterol-bearing pullulan nanogel (CHPANG) with thiol group-modified poly (ethylene glycol) (PEGSH) by Michael addition yielded A-CHPNG with narrow size distribution. The size of A-CHPNGs was controlled in the range of 40-120 nm by changing the concentration of CHPANG and PEGSH. A-CHPNG gradually degraded by hydrolysis under physiological condition and seemed to dissociate back to original nanogel. A-CHPNG encapsulated interleukin-12 (IL-12) efficiently (96\%) and stably kept it in the presence of BSA (50 mg/ml). In addition, A-CHPNG had a high potential to maintain a high IL-12 level in plasma after subcutaneous injection in mice. Therefore, A-CHPNG is a promising carrier for long-term medications.",

author = "Urara Hasegawa and Sawada, \{Shin ichi\} and Takeshi Shimizu and Tsunao Kishida and Eigo Otsuji and Osam Mazda and Kazunari Akiyoshi",

note = "Funding Information: This work was supported by the grant from the Japanese Ministry of Education, Global Center of Excellence (GCOE) Program, “International Research Center for Molecular Science in Tooth and Bone Diseases”. This work was also supported by the Japan Society for the Promotion of Science under grant-in-aid for Creative Scientific Re search (No. 18GS0421) and by the Ministry of Education, Culture, Sports, Science and Technology of Japan (20011002). We thank Mr. Masahide Nakamura (Shoko Co.) for FFF-MALS measurement. We also thank Dr. Nobuyuki Morimoto (Tokyo Medical and Dental University) for technical help and advice.",

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AU - Hasegawa, Urara

AU - Sawada, Shin ichi

AU - Shimizu, Takeshi

AU - Kishida, Tsunao

AU - Otsuji, Eigo

AU - Mazda, Osam

AU - Akiyoshi, Kazunari

N1 - Funding Information: This work was supported by the grant from the Japanese Ministry of Education, Global Center of Excellence (GCOE) Program, “International Research Center for Molecular Science in Tooth and Bone Diseases”. This work was also supported by the Japan Society for the Promotion of Science under grant-in-aid for Creative Scientific Re search (No. 18GS0421) and by the Ministry of Education, Culture, Sports, Science and Technology of Japan (20011002). We thank Mr. Masahide Nakamura (Shoko Co.) for FFF-MALS measurement. We also thank Dr. Nobuyuki Morimoto (Tokyo Medical and Dental University) for technical help and advice.

PY - 2009/12/16

Y1 - 2009/12/16

N2 - Raspberry-like assembly of nanogels (A-CHPNG) with a high potential as a carrier for protein delivery was prepared. Cross-linking of acrylate group-modified cholesterol-bearing pullulan nanogel (CHPANG) with thiol group-modified poly (ethylene glycol) (PEGSH) by Michael addition yielded A-CHPNG with narrow size distribution. The size of A-CHPNGs was controlled in the range of 40-120 nm by changing the concentration of CHPANG and PEGSH. A-CHPNG gradually degraded by hydrolysis under physiological condition and seemed to dissociate back to original nanogel. A-CHPNG encapsulated interleukin-12 (IL-12) efficiently (96%) and stably kept it in the presence of BSA (50 mg/ml). In addition, A-CHPNG had a high potential to maintain a high IL-12 level in plasma after subcutaneous injection in mice. Therefore, A-CHPNG is a promising carrier for long-term medications.

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Raspberry-like assembly of cross-linked nanogels for protein delivery

Abstract

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