Integrated platform for brain imaging and drug delivery across the blood-brain barrier

Methods Mol Biol. 2011;686:465-81. doi: 10.1007/978-1-60761-938-3_24.

Abstract

The development of imaging and therapeutic agents against neuronal targets is hampered by the limited access of probes into the central nervous system across the blood-brain barrier (BBB). The evaluation of drug penetration into the brain in experimental models often requires complex procedures, including drug radiolabeling, as well as determinations in multiple animals for each condition or time point. Prospective in vivo imaging of drug biodistribution may provide an alternative to "classical" pharmacokinetics and biodistribution studies in that a contrast-enhanced imaging signal could serve as a surrogate for the amount of drug or biologic delivered to the organ of interest. For the brain-targeting applications, it is necessary to develop formulation strategies that enable a simultaneous drug and contrast agent delivery across the BBB. In this chapter, we describe methods for encapsulating drugs into liposome nanocarriers with surface display of both the imaging contrast agent for one or multiple imaging modalities and the single-domain antibody that undergoes receptor-mediated transcytosis across the BBB. Contrast-enhanced imaging signal detected in the brain after intravenous injection of such formulation(s) is proportional to the amount of drug delivered into the brain parenchyma. This method allows for a prospective, noninvasive estimation of drug delivery, accumulation, and elimination from the brain.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / metabolism
  • Antineoplastic Agents / pharmacology
  • Blood-Brain Barrier / drug effects*
  • Blood-Brain Barrier / metabolism*
  • Brain Mapping*
  • Brain Neoplasms / blood supply*
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / metabolism
  • Contrast Media / metabolism
  • Doxorubicin / administration & dosage
  • Doxorubicin / metabolism
  • Doxorubicin / pharmacology
  • Drug Delivery Systems*
  • Liposomes / chemical synthesis
  • Liposomes / chemistry
  • Liposomes / metabolism
  • Mice
  • Nanoparticles

Substances

  • Antineoplastic Agents
  • Contrast Media
  • Liposomes
  • Doxorubicin