title: Core-shell structure of degradable, thermosensitive polymeric micelles studied by small-angle neutron scattering.
abstract: The structure of assemblies of block copolymers composed of thermosensitive, biodegradable poly(N-(2-hydroxypropyl) methacrylamide-dilactate) and poly(ethylene glycol) (pHPMAmDL-b-PEG) has been studied by small-angle neutron scattering (SANS). Three amphiphilic copolymers with a fixed PEG of 5 kDa and a partially deuterated pHPMAmDL(d) block of 6700, 10400, or 21200 Da were used to form micelles in aqueous media by heating the polymeric solution from below to above the cloud point temperature (around 10 degrees C) of the thermosensitive block. Simultaneous and quantitative analysis of the scattering cross sections obtained at three different solvent contrasts is expedited using core-shell model, which assumed a homogeneous core of uniform scattering length density. The mean core radius increased from 13 to 18.5 nm with the molecular weight of the pHPMAmDL(d) block, while the thickness of the stabilizing PEG layer was around 8 nm for the three investigated assemblies. In addition, the volume fraction values of the stabilizing PEG chains in the shell are low and decreased from 31% to 14% with increasing the size of pHPMAmDL(d) block which shows that the shell layer of the assemblies is highly hydrated. The corresponding PEG chain grafting densities decreased from 0.22 to 0.11 nm-2 and the distance between PEG chains on the nanoparticles surface increased from 2.4 to 3.4 nm. The pHPMAmDL-b-PEG micelles showed a controlled instability due to hydrolysis of the lactic acid side groups in the thermosensitive block; that is, an increase of the degradation time leads to an increase of the size of the core which becomes less hydrophobic and consequently more hydrated. Neutron experiments supplied accurate information on how the size of the core and the micelle's aggregation number changed with the incubation time. This feature and the initially small size and dense structure in aqueous solution make the polymeric micelles suitable as carriers for hydrophobic drugs.
authors.affiliation: Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Faculty of Pharmaceutical Sciences, Utrecht University, The Netherlands.
authors.forename: Aissa
authors.initials: A
authors.lastname: Ramzi
authors.forename: Cristianne J F
authors.initials: CJ
authors.lastname: Rijcken
authors.forename: Theo F J
authors.initials: TF
authors.lastname: Veldhuis
authors.forename: Dietmar
authors.initials: D
authors.lastname: Schwahn
authors.forename: Wim E
authors.initials: WE
authors.lastname: Hennink
authors.forename: Cornelus F
authors.initials: CF
authors.lastname: van Nostrum
mesh_terms: D000178:Acrylamides / Q000737:chemistry*; D001672:Biocompatible Materials / Q000737:chemistry*; D006868:Hydrolysis; D057927:Hydrophobic and Hydrophilic Interactions; D007773:Lactates / Q000737:chemistry*; D008823:Micelles; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry*; D053838:Scattering, Small Angle; D012995:Solubility; D013499:Surface Properties; D013696:Temperature; D013997:Time Factors; D014867:Water / Q000737:chemistry
chemical_list: D000178:Acrylamides; D001672:Biocompatible Materials; D007773:Lactates; D008823:Micelles; C509680:poly(N-(2-hydroxypropyl) methacrylamide lactate); D014867:Water; D011092:Polyethylene Glycols