The synthesis of a multiblock osteotropic polyrotaxane by copper(I)-catalyzed huisgen 1,3-dipolar cycloaddition.
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.
Department of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, 986025 Nebraska Medical Center, Omaha, Nebraska 68198-6025, USA.
Christopher D
CD
Hein
Xin-Ming
XM
Liu
Fu
F
Chen
Diane M
DM
Cullen
Dong
D
Wang
D019386:Alendronate / Q000378:metabolism* / Q000494:pharmacology; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism*; D002850:Chromatography, Gel; D002851:Chromatography, High Pressure Liquid; D003505:Cyclodextrins / Q000138:chemical synthesis* / Q000378:metabolism; D016503:Drug Delivery Systems / Q000379:methods*; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D020442:Poloxamer / Q000138:chemical synthesis* / Q000378:metabolism; D011092:Polyethylene Glycols / Q000378:metabolism; D058105:Polymerization; D043862:Rotaxanes / Q000138:chemical synthesis* / Q000378:metabolism; D047391:alpha-Cyclodextrins / Q000378:metabolism
D003505:Cyclodextrins; D043862:Rotaxanes; D047391:alpha-Cyclodextrins; C475673:polyrotaxane; D020442:Poloxamer; D011092:Polyethylene Glycols; D019386:Alendronate; C032613:alpha-cyclodextrin