title: Progesterone binding nano-carriers based on hydrophobically modified hyperbranched polyglycerols.
abstract: Progesterone (Pro) is a potent neurosteroid and promotes recovery from moderate Traumatic Brain Injury but its clinical application is severely impeded by its poor water solubility. Here we demonstrate that reversibly binding Pro within hydrophobically modified hyperbranched polyglycerol (HPG-Cn-MPEG) enhances its solubility, stability and bioavailability. Synthesis, characterization and Pro loading into HPG-Cn-MPEG is described. The release kinetics are correlated with structural properties and the results of Differential Scanning Calorimetry studies of a family of HPG-Cn-MPEGs of varying molecular weight and alkylation. While the maximum amount of Pro bound correlates well with the amount of alkyl carbon per molecule contributing to its hydrophobicity, the dominant first order rate constant for Pro release correlates strongly with the amount of structured or bound water in the dendritic domain of the polymer. The results provide evidence to justify more detailed studies of interactions with biological systems, both single cells and in animal models.
authors.affiliation: Centre for Blood Research and Departments of Chemistry, University of British Columbia, Vancouver, BC, Canada V6T 1Z3.
authors.forename: M
authors.initials: M
authors.lastname: Alizadeh Noghani
authors.affiliation: Centre for Blood Research and Departments of Chemistry, University of British Columbia, Vancouver, BC, Canada V6T 1Z3 and Centre for Blood Research and Departments of Chemistry and of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada V6T 1Z3. don.brooks@ubc.ca.
authors.forename: D E
authors.initials: DE
authors.lastname: Brooks
mesh_terms: D003692:Delayed-Action Preparations / Q000737:chemistry / Q000493:pharmacokinetics; D005990:Glycerol / Q000737:chemistry*; D057927:Hydrophobic and Hydrophilic Interactions; D053758:Nanoparticles / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry*; D011374:Progesterone / Q000737:chemistry* / Q000493:pharmacokinetics*
chemical_list: D003692:Delayed-Action Preparations; D011108:Polymers; C043941:polyglycerol; D011374:Progesterone; D005990:Glycerol