Preparation and therapeutic efficacy of polysorbate-80-coated amphotericin B/PLA-b-PEG nanoparticles

J Biomater Sci Polym Ed. 2009;20(10):1369-80. doi: 10.1163/092050609X12457418779185.

Abstract

Amphotericin B (AmB)/poly(lactic acid)-b-poly(ethylene glycol) (PLA-b-PEG) nanoparticles coated with polysorbate 80 (Tween-80) were prepared by nanoprecipitation for transport across the blood-brain barrier (BBB). The effects of Tween-80 on the size and distribution, entrapment efficiency and release behavior of AmB/PLA-b-PEG nanoparticles were investigated. Furthermore, the brain targeting and curative effect of coated nanoparticles were also investigated. The entrapment efficiency was significantly enhanced when nanoparticles were coated with Tween-80. The prepared nanoparticles were spherical with homogeneous distribution. Drug concentration in mice brain was greatly enhanced, which indicated that the coated nanoparticles could get across the BBB. Meanwhile, the AmB/PLA-b-PEG nanoparticles are able to reduce the toxicity of AmB to liver, kidney and blood system with improved therapeutic effect.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amphotericin B / administration & dosage*
  • Amphotericin B / adverse effects
  • Amphotericin B / pharmacokinetics
  • Amphotericin B / therapeutic use*
  • Animals
  • Anti-Infective Agents / administration & dosage*
  • Anti-Infective Agents / adverse effects
  • Anti-Infective Agents / pharmacokinetics
  • Anti-Infective Agents / therapeutic use*
  • Blood-Brain Barrier / metabolism
  • Brain / drug effects
  • Brain / metabolism
  • Cryptococcus neoformans / drug effects
  • Drug Carriers / chemistry
  • Hematologic Tests
  • Kidney / drug effects
  • Kidney / metabolism
  • Lactates / chemistry*
  • Liver / drug effects
  • Liver / metabolism
  • Meningitis, Cryptococcal / drug therapy
  • Mice
  • Mice, Inbred BALB C
  • Nanoparticles / chemistry*
  • Nanoparticles / ultrastructure
  • Polyethylene Glycols / chemistry*
  • Polysorbates / chemistry*

Substances

  • Anti-Infective Agents
  • Drug Carriers
  • Lactates
  • Polysorbates
  • poly(lactic acid-ethylene glycol)
  • Polyethylene Glycols
  • Amphotericin B