title: Efficient encapsulation of a water-soluble corticosteroid in biodegradable nanoparticles.
abstract: Solid nanoparticles consisting of biodegradable polymers have emerged as a promising carrier for various drugs, but unfortunately the encapsulation of drugs remains challenging. In this study, a technique for encapsulation of water-soluble drugs in solid nanoparticles was developed. Nanoparticles were prepared from a blend of biodegradable polymers, including poly(lactic acid) (PLA) and poly(lactic/glycolic acid) (PLGA), and monomethoxypolyethyleneglycol-polylactide block copolymer by an oil-in-water solvent diffusion method. Betamethasone sodium phosphate (BP) was not encapsulated by the nanoparticles due to its hydrophilicity, but it was effectively encapsulated in the presence of appropriate amounts of zinc and diethanolamine. It was found that BP formed an ionic complex with zinc at a certain pH range obtained by addition of diethanolamine. Furthermore, a carboxyl group located at the end of PLA/PLGA was shown to be essential for encapsulation of BP in nanoparticles, and the molar ratio among BP, zinc, and carboxyl groups in various nanoparticles was almost constant. These results strongly suggested that the encapsulation was promoted by zinc creating an ionic bridge between a carboxyl group on PLA/PLGA and a phosphate group on BP. This technique for entrapment of water-soluble drugs in solid biodegradable nanoparticles may expand the use of nanoparticles 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: Miyuki
authors.initials: M
authors.lastname: Takahashi
authors.forename: Megumu
authors.initials: M
authors.lastname: Higaki
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Mizushima
mesh_terms: D001623:Betamethasone / Q000031:analogs & derivatives* / Q000737:chemistry; D002626:Chemistry, Pharmaceutical; D002712:Chlorides / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry*; D004983:Ethanolamines / Q000737:chemistry; D005938:Glucocorticoids / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D019344:Lactic Acid / Q000737:chemistry; D053758:Nanoparticles; D011091:Polyesters / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000737:chemistry*; D012995:Solubility; D017967:Zinc Compounds / Q000737:chemistry
chemical_list: D002712:Chlorides; D004337:Drug Carriers; D004983:Ethanolamines; D005938:Glucocorticoids; D011091:Polyesters; D011108:Polymers; D017967:Zinc Compounds; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D011092:Polyethylene Glycols; C033616:poly(lactide); C028994:betamethasone sodium phosphate; C016837:zinc chloride; C028210:monomethoxypolyethylene glycol; D001623:Betamethasone; C020283:diethanolamine