title: In vitro and in vivo characterization of nanoparticles made of MeO-PEG amine/PLA block copolymer and PLA.
abstract: The preparative method of a block copolymer of poly(dl-lactic acid) (PLA) and methoxypolyethylene glycol amine (MeO-PEG(N)), named PLA-(MeO-PEG), was refined. The degree of introduction of MeO-PEG(N) into PLA increased up to 55% (mol/mol) using a dichloromethane/methanol mixture (1:1, v/v) as a solvent at the reductive amination and taking all the fractions of the first peak in gel-chromatography. Plain and 1,1'-Dioctadecyl-3,3,3',3'-tetramethylindodicarbocyanine (DiD)-loaded nanoparticles prepared using the PLA/PLA-(MeO-PEG) mixture of 45:55 (mol/mol) showed a mean size of 113 and 154 nm, respectively, and a positive zeta potential in water. DiD solution, i.v. administered, showed a lower plasma level and high distribution in liver, though DiD was distributed into the blood cells to a fair extent. Nanoparticles exhibited a higher plasma concentration of DiD than the DiD solution at 1 and 8h, though DiD was distributed into the liver and spleen to a fair extent. Nanoparticles made of the PLA/PLA-(MeO-PEG) mixture of 44:55 (mol/mol) showed better plasma retention than those made of the PLA/PLA-(MeO-PEG) mixture of 64:36 (mol/mol). It is suggested that the PLA/PLA-(MeO-PEG) mixture nanoparticles with a higher PEG/PLA ratio should be useful as a carrier for the elevation of the plasma concentration of lipophilic drugs.
authors.affiliation: Department of Drug Delivery Research, Hoshi University, 2-4-41, Ebara, Shinagawa-ku, Tokyo 142-8501, Japan.
authors.forename: Masanaho
authors.initials: M
authors.lastname: Sasatsu
authors.forename: Hiraku
authors.initials: H
authors.lastname: Onishi
authors.forename: Yoshiharu
authors.initials: Y
authors.lastname: Machida
mesh_terms: D000818:Animals; D001773:Blood Cells / Q000378:metabolism; D002232:Carbocyanines / Q000737:chemistry / Q000493:pharmacokinetics*; D004337:Drug Carriers / Q000737:chemistry; D005456:Fluorescent Dyes / Q000737:chemistry / Q000493:pharmacokinetics*; D019344:Lactic Acid / Q000737:chemistry*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D049329:Nanostructures / Q000737:chemistry; D010949:Plasma / Q000378:metabolism; D011091:Polyesters; D011092:Polyethylene Glycols / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry*; D014018:Tissue Distribution
chemical_list: D002232:Carbocyanines; D004337:Drug Carriers; D005456:Fluorescent Dyes; D011091:Polyesters; D011108:Polymers; C401288:methoxy polyethylene glycol amine; D019344:Lactic Acid; D011092:Polyethylene Glycols; C024286:3,3'-dioctadecylindocarbocyanine; C033616:poly(lactide)