title: Self-assembled pH-sensitive cholesteryl pullulan nanogel as a protein delivery vehicle.
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.
authors.affiliation: Department of Materials Processing, Graduate School of Engineering, Tohoku University, 6-6-02 Aramaki-aza Aoba, Aoba-ku, Sendai 980-8579, Japan.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Morimoto
authors.forename: Sayaka
authors.initials: S
authors.lastname: Hirano
authors.forename: Haruko
authors.initials: H
authors.lastname: Takahashi
authors.forename: Scott
authors.initials: S
authors.lastname: Loethen
authors.forename: David H
authors.initials: DH
authors.lastname: Thompson
authors.forename: Kazunari
authors.initials: K
authors.lastname: Akiyoshi
mesh_terms: D000818:Animals; D002417:Cattle; D002784:Cholesterol / Q000008:administration & dosage / Q000737:chemistry*; D016503:Drug Delivery Systems / Q000379:methods*; D005936:Glucans / Q000008:administration & dosage / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D000080385:Nanogels; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000737:chemistry*; D011094:Polyethyleneimine / Q000008:administration & dosage / Q000737:chemistry*; D012710:Serum Albumin, Bovine / Q000008:administration & dosage / Q000737:chemistry*
chemical_list: D005936:Glucans; D000080385:Nanogels; C413692:polyethylene glycol polyethyleneimine nanogel; D012710:Serum Albumin, Bovine; D011092:Polyethylene Glycols; C009109:pullulan; D011094:Polyethyleneimine; D002784:Cholesterol