Active brain targeting of a fluorescent P-gp substrate using polymeric magnetic nanocarrier system

Nanotechnology. 2012 Jun 29;23(25):255102. doi: 10.1088/0957-4484/23/25/255102. Epub 2012 May 31.

Abstract

Magnetic nanoparticles (NP) were developed for the active brain targeting of water-soluble P-glycoprotein (P-gp) substrate rhodamine 123 (Rh123). The NP matrix of poly(lactide-co-glycolide) (PLGA) and methoxy poly(ethyleneglycol)-poly(lactic acid) (M-PEG-PLA) was prepared by single emulsion solvent evaporation of polymers with oleic acid-coated magnetic nanoparticles (OAMNP) and Rh123. All formulations were characterized in terms of morphology, particle size, magnetic content and Rh123 encapsulation efficiency. The maximum encapsulation efficiency of Rh123 was 45 ± 3% and of OAMNP was 42 ± 4%. The brain targeting and biodistribution study was performed on Sprague Dawley rats (3 groups, n = 6). Rh123 (0.4 mg kg(-1)) was administered in saline form, NP containing Rh123, and NP containing Rh123 in the presence of a magnetic field (0.8 T). The fluorimetric analysis of brain homogenates revealed a significant uptake (p < 0.05) of Rh123 in the magnetically targeted group relative to controls. These results were supported by fluorescence microscopy. This study reveals the ability of magnetically targeted nanoparticles to deliver substances to the brain, the permeation of which would otherwise be inhibited by the P-gp system.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / chemistry
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism*
  • Animals
  • Brain / metabolism*
  • Brain Chemistry
  • Drug Carriers / chemistry
  • Drug Carriers / pharmacokinetics*
  • Drug Delivery Systems
  • Fluorescent Dyes / chemistry
  • Fluorescent Dyes / pharmacokinetics*
  • Histocytochemistry
  • Lactic Acid / chemistry
  • Magnetite Nanoparticles / chemistry*
  • Male
  • Microscopy, Fluorescence
  • Oleic Acid / chemistry
  • Polyethylene Glycols / chemistry
  • Polyglycolic Acid / chemistry
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Rats
  • Rats, Sprague-Dawley
  • Rhodamine 123 / chemistry
  • Rhodamine 123 / pharmacokinetics
  • Tissue Distribution

Substances

  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Drug Carriers
  • Fluorescent Dyes
  • Magnetite Nanoparticles
  • monomethoxypolyethyleneglycol-polylactide block copolymer
  • Rhodamine 123
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Polyglycolic Acid
  • Oleic Acid
  • Lactic Acid
  • Polyethylene Glycols