Medicinal chemistry based approaches and nanotechnology-based systems to improve CNS drug targeting and delivery

Med Res Rev. 2013 May;33(3):457-516. doi: 10.1002/med.21252. Epub 2012 Mar 20.

Abstract

The central nervous system (CNS) is protected by various barriers, which regulate nervous tissue homeostasis and control the selective and specific uptake, efflux, and metabolism of endogenous and exogenous molecules. Among these barriers is the blood-brain barrier (BBB), a physical and physiological barrier that filters very efficiently and selectively the entry of compounds from the blood to the brain and protects nervous tissue from harmful substances and infectious agents present in the bloodstream. The BBB also prevents the entry of potential drugs. As a result, various drug targeting and delivery strategies are currently being developed to enhance the transport of drugs from the blood to the brain. Following a general introduction, we briefly overview in this review article the fundamental physiological properties of the BBB. Then, we describe current strategies to bypass the BBB (i.e., invasive methods, alternative approaches, and temporary opening) and to cross it (i.e., noninvasive approaches). This section is followed by a chapter addressing the chemical and technological solutions developed to cross the BBB. A special emphasis is given to prodrug-targeting approaches and targeted nanotechnology-based systems, two promising strategies for BBB targeting and delivery of drugs to the brain.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / antagonists & inhibitors
  • Blood-Brain Barrier / physiology*
  • Brain / metabolism
  • Central Nervous System Agents / administration & dosage
  • Central Nervous System Agents / therapeutic use*
  • Central Nervous System Diseases / drug therapy
  • Diffusion
  • Drug Carriers / metabolism
  • Drug Delivery Systems / methods
  • Endocytosis
  • Humans
  • Liposomes / administration & dosage
  • Nanotechnology
  • Prodrugs / metabolism

Substances

  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Central Nervous System Agents
  • Drug Carriers
  • Liposomes
  • Prodrugs