The synthesis of a multiblock osteotropic polyrotaxane by copper(I)-catalyzed huisgen 1,3-dipolar cycloaddition

Macromol Biosci. 2010 Dec 8;10(12):1544-56. doi: 10.1002/mabi.201000205. Epub 2010 Oct 15.

Abstract

The design and synthesis of a novel bone-targeting polyrotaxane delivery system that utilizes alendronate (ALN) as targeting moiety is presented in this manuscript. For the introduction of ALN, it is first conjugated to α-cyclodextrin (α-CD) and subsequently threaded onto a short poly(ethylene glycol) (PEG) chain, forming a pseudopolyrotaxane. Using click chemistry, this assembly is copolymerized with bulky monomers that bear imaging and/or therapeutic agent(s) to prevent ALN-functionalized α-CD from dethreading. Overall bone affinity of this novel polymer conjugate can be easily controlled by changing the number of ALN-α-CD incorporated. The osteotropicity of the delivery system was also confirmed in vivo.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alendronate / metabolism*
  • Alendronate / pharmacology
  • Bone and Bones / drug effects
  • Bone and Bones / metabolism*
  • Chromatography, Gel
  • Chromatography, High Pressure Liquid
  • Cyclodextrins / chemical synthesis*
  • Cyclodextrins / metabolism
  • Drug Delivery Systems / methods*
  • Magnetic Resonance Spectroscopy
  • Molecular Structure
  • Poloxamer / chemical synthesis*
  • Poloxamer / metabolism
  • Polyethylene Glycols / metabolism
  • Polymerization
  • Rotaxanes / chemical synthesis*
  • Rotaxanes / metabolism
  • alpha-Cyclodextrins / metabolism

Substances

  • Cyclodextrins
  • Rotaxanes
  • alpha-Cyclodextrins
  • polyrotaxane
  • Poloxamer
  • Polyethylene Glycols
  • Alendronate
  • alpha-cyclodextrin