Ultrasound-sensitive nanoparticle aggregates for targeted drug delivery

Biomaterials. 2017 Sep;139:187-194. doi: 10.1016/j.biomaterials.2017.06.003. Epub 2017 Jun 6.

Abstract

Here we describe injectable, ultrasound (US)-responsive, nanoparticle aggregates (NPAs) that disintegrate into slow-release, nanoscale, drug delivery systems, which can be targeted to selective sites by applying low-energy US locally. We show that, unlike microbubble based drug carriers which may suffer from stability problems, the properties of mechanical activated NPAs, composed of polymer nanoparticles, can be tuned by properly adjusting the polymer molecular weight, the size of the nanoparticle precursors as well as the percentage of excipient utilized to hold the NPA together. We then apply this concept to practice by fabricating NPAs composed of nanoparticles loaded with Doxorubicin (Dox) and tested their ability to treat tumors via ultrasound activation. Mouse studies demonstrated significantly increased efficiency of tumor targeting of the US-activated NPAs compared to PLGA nanoparticle controls (with or without US applied) or intact NPAs. Importantly, when the Dox-loaded NPAs were injected and exposed to US energy locally, this increased ability to concentrate nanoparticles at the tumor site resulted in a significantly greater reduction in tumor volume compared to tumors treated with a 20-fold higher dose of the free drug.

Keywords: Doxorubicin; Drug release; PLGA nanoparticles; Tumor targeting; Ultrasound.

MeSH terms

  • Animals
  • Biocompatible Materials / administration & dosage
  • Cell Line, Tumor
  • Doxorubicin / administration & dosage
  • Doxorubicin / chemistry
  • Drug Carriers / administration & dosage
  • Drug Delivery Systems*
  • Drug Liberation*
  • Excipients
  • Lactic Acid / administration & dosage
  • Mice
  • Mice, Inbred BALB C
  • Microbubbles
  • Molecular Weight
  • Nanoparticles / administration & dosage
  • Nanoparticles / chemistry*
  • Neoplasms / drug therapy*
  • Particle Size
  • Polyglycolic Acid / administration & dosage
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Polymers / chemistry
  • Ultrasonics

Substances

  • Biocompatible Materials
  • Drug Carriers
  • Excipients
  • Polymers
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Polyglycolic Acid
  • Lactic Acid
  • Doxorubicin