Self-assembled pH-sensitive cholesteryl pullulan nanogel as a protein delivery vehicle

Nobuyuki Morimoto; Sayaka Hirano; Haruko Takahashi; Scott Loethen; David H. Thompson; Kazunari Akiyoshi

doi:10.1021/bm301286h

Self-assembled pH-sensitive cholesteryl pullulan nanogel as a protein delivery vehicle

Nobuyuki Morimoto, Sayaka Hirano, Haruko Takahashi, Scott Loethen, David H. Thompson, Kazunari Akiyoshi

ENG - Materials Processing

Research output: Contribution to journal › Article

90 Citations (Scopus)

Abstract

A self-assembled nanogel, derived from an acid-labile cholesteryl-modified pullulan (acL-CHP), was prepared by grafting vinyl ether-cholesterol substituents onto a 100 kD pullulan main chain polymer backbone. Stable nanogels are formed by acL-CHP self-assemblies at neutral pH. The hydrodynamic radius of the nanogels, observed to be 26.5 ± 5.1 nm at pH 7.0, increased by ∼135% upon acidification of the solution to pH 4.0. SEC analysis of the acL-CHP nanogel at pH 4.0 showed that the grafts were nearly 80% degraded after 24 h, whereas little or no degradation was observed over the same time period for a pH stable analog (acS-CHP) at pH 4.0 or the acL-CHP at pH 7.0. Complexation of BSA with the acL-CHP nanogel was observed at pH 7.0 with subsequent release of the protein upon acidification. These findings suggest that stimuli-responsive, self-assembled nanogels can release protein cargo in a manner that is controlled by the degradation rate of the cholesterol-pullulan grafting moiety.

Original language	English
Pages (from-to)	56-63
Number of pages	8
Journal	Biomacromolecules
Volume	14
Issue number	1
DOIs	https://doi.org/10.1021/bm301286h
Publication status	Published - 2013 Jan 14

ASJC Scopus subject areas

Bioengineering
Biomaterials
Polymers and Plastics
Materials Chemistry

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Morimoto, N., Hirano, S., Takahashi, H., Loethen, S., Thompson, D. H., & Akiyoshi, K. (2013). Self-assembled pH-sensitive cholesteryl pullulan nanogel as a protein delivery vehicle. Biomacromolecules, 14(1), 56-63. https://doi.org/10.1021/bm301286h

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abstract = "A self-assembled nanogel, derived from an acid-labile cholesteryl-modified pullulan (acL-CHP), was prepared by grafting vinyl ether-cholesterol substituents onto a 100 kD pullulan main chain polymer backbone. Stable nanogels are formed by acL-CHP self-assemblies at neutral pH. The hydrodynamic radius of the nanogels, observed to be 26.5 ± 5.1 nm at pH 7.0, increased by ∼135% upon acidification of the solution to pH 4.0. SEC analysis of the acL-CHP nanogel at pH 4.0 showed that the grafts were nearly 80% degraded after 24 h, whereas little or no degradation was observed over the same time period for a pH stable analog (acS-CHP) at pH 4.0 or the acL-CHP at pH 7.0. Complexation of BSA with the acL-CHP nanogel was observed at pH 7.0 with subsequent release of the protein upon acidification. These findings suggest that stimuli-responsive, self-assembled nanogels can release protein cargo in a manner that is controlled by the degradation rate of the cholesterol-pullulan grafting moiety.",

author = "Nobuyuki Morimoto and Sayaka Hirano and Haruko Takahashi and Scott Loethen and Thompson, {David H.} and Kazunari Akiyoshi",

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AU - Thompson, David H.

AU - Akiyoshi, Kazunari

PY - 2013/1/14

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N2 - A self-assembled nanogel, derived from an acid-labile cholesteryl-modified pullulan (acL-CHP), was prepared by grafting vinyl ether-cholesterol substituents onto a 100 kD pullulan main chain polymer backbone. Stable nanogels are formed by acL-CHP self-assemblies at neutral pH. The hydrodynamic radius of the nanogels, observed to be 26.5 ± 5.1 nm at pH 7.0, increased by ∼135% upon acidification of the solution to pH 4.0. SEC analysis of the acL-CHP nanogel at pH 4.0 showed that the grafts were nearly 80% degraded after 24 h, whereas little or no degradation was observed over the same time period for a pH stable analog (acS-CHP) at pH 4.0 or the acL-CHP at pH 7.0. Complexation of BSA with the acL-CHP nanogel was observed at pH 7.0 with subsequent release of the protein upon acidification. These findings suggest that stimuli-responsive, self-assembled nanogels can release protein cargo in a manner that is controlled by the degradation rate of the cholesterol-pullulan grafting moiety.

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