Novel multiple agents loaded PLGA nanoparticles for brain delivery via inner ear administration: in vitro and in vivo evaluation

Eur J Pharm Sci. 2013 Mar 12;48(4-5):595-603. doi: 10.1016/j.ejps.2013.01.007. Epub 2013 Jan 23.


The aim of this study was to develop novel multiple agents loaded poly (D,L-lactide-co-glycolide acid) (PLGA) nanoparticles (NPs) and evaluate their potential for brain delivery via inner ear administration. PLGA NPs loaded with salvianolic acid B (Sal B), tanshinone IIA (TS IIA) and panax notoginsenoside (PNS) were prepared by double emulsion/solvent evaporation method. It was observed that optimized NPs displayed satisfactory encapsulation efficiency and desired sustained-release characteristics. NPs following intratympanic administration (IT) in guinea pigs greatly improved drug distribution within the inner ear, cerebrospinal fluid (CSF) and brain tissues compared with intravenous administration (IV). Pharmacodynamic studies demonstrated that NPs following IT markedly inhibited oxidizing reactions and protected the brain from cerebral ischemia reperfusion (I/R) injury by upregulating superoxide dismutase (SOD) activity both in serum and brain tissues, simultaneously significantly reducing the levels of malondialdehyde (MDA) and nitric oxide synthase (NOS). Moreover intratympanic delivery did not cause injury of cochlear function by preliminary study on the toxicity. These findings suggested that PLGA NPs-based delivery system via inner ear administration was a promising candidate to brain delivery for the treatment of brain diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abietanes / administration & dosage*
  • Abietanes / cerebrospinal fluid
  • Abietanes / pharmacokinetics
  • Animals
  • Benzofurans / administration & dosage*
  • Benzofurans / cerebrospinal fluid
  • Benzofurans / pharmacokinetics
  • Brain / metabolism
  • Carotid Arteries
  • Drug Administration Routes
  • Drug Carriers / administration & dosage*
  • Drug Carriers / chemistry
  • Drug Carriers / pharmacokinetics
  • Ear, Inner
  • Ginsenosides / administration & dosage*
  • Ginsenosides / cerebrospinal fluid
  • Ginsenosides / pharmacokinetics
  • Guinea Pigs
  • Lactic Acid / administration & dosage
  • Lactic Acid / chemistry
  • Male
  • Nanoparticles / administration & dosage*
  • Nanoparticles / chemistry
  • Neuroprotective Agents / administration & dosage
  • Neuroprotective Agents / cerebrospinal fluid
  • Neuroprotective Agents / pharmacokinetics
  • Panax notoginseng
  • Particle Size
  • Polyglycolic Acid / administration & dosage
  • Polyglycolic Acid / chemistry
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Reperfusion Injury / drug therapy*
  • Reperfusion Injury / metabolism


  • Abietanes
  • Benzofurans
  • Drug Carriers
  • Ginsenosides
  • Neuroprotective Agents
  • tanshinone
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Polyglycolic Acid
  • Lactic Acid
  • salvianolic acid B