Microscopic Structure and Thermoresponsiveness of a Hydrogel Nanoparticle by Self-Assembly of a Hydrophobized Polysaccharide

Abstract

Various cholesterol-bearing pullulans (CHPs) with different molecular weights of the parent pullulan and degrees of substitution (DS) of the cholesteryl moiety were synthesized. The structural characteristics of CHPs in water were studied by static (SLS) and dynamic light scattering (DLS) and the fluorescence probe method. Irrespective of the molecular weight of the parent pullulan and the DS, all of CHPs provided unimodal and monodisperse self-aggregates in water. The size of the self-aggregate decreased with an increase in the DS of the cholesteryl moiety (hydrodynamic radius, 8.4−13.7 nm). However, the aggregation number of CHP in one nanoparticle was almost independent of the DS. The polysaccharide density within the self-aggregate (0.13−0.50 g/mL) was affected by both the molecular weight and the DS of CHPs. The mean aggregation number of the cholesteryl moiety (3.5−5.7), which was estimated by the fluorescence quenching method using pyrene and cetylpyridinium chloride, was almost same for all the CHP self-aggregates. The CHP self-aggregate is regarded as a hydrogel nanoparticle, in which pullulan chains are cross-linked noncovalently by associating cholesteryl moieties. The microenvironment inside or the structural characteristic of the self-aggregate was spectrometrically studied using a fluorescence probe, ANS. The characteristic temperature to cause a structural change of the nanoparticle (T*) decreased with an increase in the DS of CHP and the ionic strength of the medium. The thermoresponsiveness of the nanoparticle hydrogel is related to the partial dehydration of the hydrophobized pullulan upon heating.

Cellular uptake mechanism and intracellular fate of hydrophobically modified pullulan nanoparticles

“…5 In recent years, many studies have been carried out to investigate the synthesis and the application of pullulan-based self-assembled NPs as drug delivery systems, [6][7][8][9][10][11][12] among which, cholesterol-bearing pullulan (CHP), synthesized by the reaction between cholesteryl N-(6-isocynatohexyl)carbamate and pullulan using 1,6-hexyl diisocyanate linkages, has attracted much attention. CHP can form stable hydrogel NPs by self-assembly, 13,14 and can then form complexes with various drugs and proteins by hydrophobic interaction and release them upon exposure to specific proteins or cyclodextrin. [15][16][17][18] The hydrogel NPs can also be used as a drug carrier system in medicine 17,19,20 as well as artificial molecular chaperones in biotechnology.…”

Preparation and Characterizations of Poly(ethylene glycol)-Poly(ε-caprolactone) Block Copolymer Nanoparticles

“…10,11 Therefore, a number of studies have focused on the applications of the polymeric micelles and/or nanoparticles into cancer drug delivery systems. 8,[10][11][12][13][14] As nanoparticle forming materials, amphiphilic block copolymers, 4,6-9,11-13 hydrophobically modified water-soluble polymers, [15][16][17] and hydrophobized polysaccharides 3,14,18,19 have been extensively investigated. In this study, we focused on the PEG-PCL diblock copolymers.…”

Nanoparticles Based on Modified Polysaccharides

“…It was designed as a self-aggregate to form monodisperse and stable nanogels due to the hydrophobic moieties in an aqueous solution. The nanogels formed complexes with various drugs and proteins by hydrophobic interaction and released them upon exposure to specific proteins (Akiyoshi et al, 1997;Akiyoshi et al, 1993;Cheng et al, 2008). Hydrophobically-modified pullulans of moderate molar mass and differing in hydrophobic modification ratio, charge ratio and the nature of the hydrophobic chains were prepared (Bataille et al, 1997;Glinel et al, 1999;Fischer et al, 1998).…”

“…Various cholesterol-bearing pullulans with different MWs of the parent pullulan and DS of the cholesteryl moiety was synthesized (Nishikawa et al, 1996;Akiyoshi et al, 1997). Irrespective of the MW of the parent pullulan and the DS, all of cholesterol-pullulans provided unimodal and mono-disperse self-aggregates in water.…”