title: Nanoparticle processing in the solid state dramatically increases the cell membrane permeation of a cholesterol-lowering drug, probucol.
abstract: High cholesterol levels (or hypercholesterolemia) are linked with many diseases, particularly with the risk of coronary heart diseases. Probucol is commonly used to reduce cholesterol in blood. While the effectiveness of this drug highly depends on its solubility, unfortunately, it is nearly insoluble (solubility is 5 ng/mL in water). Therefore, it is essential to develop approaches to increase its solubility and bioavailability and to enhance the efficiency of the drug. Here we show that a new method increases the solubility of probucol in water and its ability to permeate cell membranes. This new method of processing the drug in a nanoparticle utilizes the grinding of PBC probucol together with sodium dodecylsulfate and methacrylic copolymer. Solid-state NMR experiments reveal the polymorphic state of probucol and the conversion of this drug from crystalline to the amorphous state, and determine its nearness to the copolymer due to the grinding process that enables the formation of nanoparticles.
authors.affiliation: College of Pharmacy, Nihon University, Chiba 274-8555, Japan. fukami.toshiro@nihon-u.ac.jp
authors.forename: Toshiro
authors.initials: T
authors.lastname: Fukami
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Ishii
authors.forename: Takeshi
authors.initials: T
authors.lastname: Io
authors.forename: Naoto
authors.initials: N
authors.lastname: Suzuki
authors.forename: Toyofumi
authors.initials: T
authors.lastname: Suzuki
authors.forename: Kazutoshi
authors.initials: K
authors.lastname: Yamamoto
authors.forename: Jiadi
authors.initials: J
authors.lastname: Xu
authors.forename: Ayyalusamy
authors.initials: A
authors.lastname: Ramamoorthy
authors.forename: Kazuo
authors.initials: K
authors.lastname: Tomono
mesh_terms: D000924:Anticholesteremic Agents / Q000378:metabolism* / Q000494:pharmacology*; D018938:Caco-2 Cells; D002463:Cell Membrane Permeability / Q000187:drug effects*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008962:Models, Theoretical; D053758:Nanoparticles / Q000737:chemistry; D011341:Probucol / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D012995:Solubility
chemical_list: D000924:Anticholesteremic Agents; D011341:Probucol