title: Efficient entrapment of poorly water-soluble pharmaceuticals in hybrid nanoparticles.
abstract: Polymeric micelles consisting of amphiphilic block copolymers have emerged as a promising carrier of various drugs, but unfortunately show a limited potential for encapsulating (solubilizing) such drugs. In this study, hybrid nanoparticles consisting of monomethoxypolyethyleneglycol-polylactide block copolymer (PEG-PLA) and oleic acid calcium salt were prepared to enhance the solubilization of poorly water-soluble drugs. Micelles made of a mixture of sodium oleate and PEG-PLA at various ratios were used as the template for preparation of the nanoparticles. These mixed micelles could efficiently solubilize poorly water-soluble drugs in aqueous media, when compared with polymeric micelles made of PEG-PLA alone. Addition of calcium to the mixed micelles induced the formation of oleic acid calcium salt, resulting in hybrid nanoparticles. These hybrid nanoparticles had a high colloidal stability, neutral zeta potential, and high drug entrapment efficiency. Drugs entrapped in nanoparticles made at a high PEG-PLA ratio were protected from enzymatic degradation in serum, while drugs entrapped in the mixed micelles were not, indicating that the hybrid nanoparticles show good drug retention. These results suggested that such hybrid nanoparticles may be used to expand the availability of poorly water-soluble drugs for various therapeutic applications.
authors.affiliation: DDS Institute, The Jikei University School of Medicine, 3-25-8 Nishi-shinbashi, Minato, Tokyo 105-8461, Japan. ishihara@jikei.ac.jp
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Ishihara
authors.forename: Maoko
authors.initials: M
authors.lastname: Goto
authors.forename: Hideko
authors.initials: H
authors.lastname: Kanazawa
authors.forename: Megumu
authors.initials: M
authors.lastname: Higaki
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Mizushima
mesh_terms: D000818:Animals; D002118:Calcium / Q000737:chemistry; D002417:Cattle; D008823:Micelles; D053758:Nanoparticles / Q000737:chemistry*; D019301:Oleic Acid / Q000737:chemistry*; D004364:Pharmaceutical Preparations / Q000737:chemistry* / Q000378:metabolism; D011092:Polyethylene Glycols / Q000737:chemistry*; D044967:Serum / Q000201:enzymology; D012995:Solubility; D014867:Water / Q000737:chemistry
chemical_list: D008823:Micelles; D004364:Pharmaceutical Preparations; C542623:monomethoxypolyethyleneglycol-polylactide block copolymer; D014867:Water; D019301:Oleic Acid; D011092:Polyethylene Glycols; D002118:Calcium