Jun 22, 2012
Sugar-based capsules deliver anticancer drugs
Capsules made from “polyrotaxanes” could make for a new type of non-toxic and efficient drug-delivery vehicle, according to researchers at the University of Melbourne in Australia. The structures studied were made up of cyclodextrins and poly(ethylene glycol), two molecules that are fully biodegradable.
A rotaxane is a mechanically interlocked structure comprising a dumbbell-shaped molecule threaded through a cyclic macromolecule. The name comes from the Latin for wheel (rota) and axle (axis). Polyrotaxanes (joined-up rotaxanes) have been little studied for drug-delivery applications but they offer great promise in this field because of their unique properties, which include the fact that they are rigid and biocompatible.
To make drug-delivery capsules, Henk Dam and Frank Caruso began by assembling polyrotaxanes on the surface of silica particle templates. The researchers then cross-linked the polyrotaxanes and removed the silica cores. The resulting spheres are equipped with alkynes, a chemical group that can be specifically reacted with a variety of molecules – such as those with so-called “stealth” properties that minimize unwanted adhesion of other substances.
The same functionalization strategy might also be used to attach antibodies to the surface of the capsules that could then specifically target diseased tissue, explains Henk Dam. The capsules themselves can be loaded with anticancer drugs, like doxorubicin.
The polyrotaxanes studied in this work are made up of cyclodextrins, which are naturally occurring cyclic sugars, and a poly(ethylene glycol) coating. Poly(ethylene glycol) is commonly found in a number of medicines and acts as the stealth molecule in this case.
“Interestingly, the sugars and the poly(ethylene glycol) have the ability to reorganize when mixed in water into a structure that looks like a necklace with beads threaded around it,” Dam told nanotechweb.org. “The beads represent the sugars and a structure like this is called a pseudopolyrotaxane. These structures can disassemble under various triggers (such as exposure to certain wavelengths of light) by the beads ‘de-threading’,” he explained. “This is an important property because any drug molecules contained within the polyrotaxane capsule, or attached to it, can then be released. What is more, the by-products of disassembling structures are harmless for the human body.”
The team, which reports its results in ACS Nano, says that it is now looking at developing other nanoengineered materials with potential therapeutic applications. “As part of this endeavour, we are developing methods to assemble materials with different architectures, such as the polyrotaxanes described in this work,” said Dam.
About the author
Belle Dumé is contributing editor at nanotechweb.org