Virus serves as model for drug carrier

by David Bradley

Tiny capsules can change size when the pH and/or the salt concentration changes, according to Swiss chemists. When the capsules swell, pores in their surface open, potentially allowing materials, such as drugs, held inside, to be released. The team believes the capsules could be used as a novel drug delivery agent that might carry biopolymers or enzymes to targeted sites in the body where they are then released.
  Marc Sauer and Wolfgang Meier of Basel University have used vesicular polymerisation to prepare water-soluble polyelectrolyte nanocapsules, which they say undergo a reversible swelling process on changing pH and/or salt concentration, mimicking certain biological processes. Nanocapsules whose size can be controlled in this way are being investigated for a wide range of applications such as confined reaction vessels, drug carriers or protective shells for cells or enzymes.
  Meier points out that, so far, most attempts to create nanocapsules have relied on non-covalent linkages to hold the container together and this makes them intrinsically unstable and so perhaps unsuitable for drug delivery. Polymers might be used to form a more robust capsule; but controlling their permeability is difficult. The cowpea chlorotic mottle virus (CCMV) uses a naturally occurring polymeric nanocontainer showing a reversible, pH-induced transition between an 'open' and a 'closed' state and the team believe it makes an excellent model for what is needed.
  The researchers have synthesised a covalently crosslinked polyelectrolyte shell which models the CCMV capsule. They have exploited the fact that the carboxylate groups of poly(acrylic acid) when used to form a hollow nanocapsule separate as pH rises because of electrostatic repulsion between the CO2- anions along the polymer backbone. This makes the particles swell considerably. They have demonstrated that the swelling is reversed as pH is lowered and suggest the stable nanocapsules might be used to carry various medicinal agents.

Chem Commun, 2001, 55-56.

Sweet drugs

A new family of inhibitors of the glycosidase enzymes have been prepared by a fusion of conduritol and carbasugar structures to form hybrids, by chemists in India. Initial analysis of the biological properties of one of these compounds reveals it to be a significant and selective alpha-glucosidase inhibitor, which bodes well for following it as a potential lead for novel diabetes and antiviral drugs.
  Conduritols and carbasugars are classes of polyhydroxylated cyclohexane-like compounds that have been pursued increasingly by synthetic chemists in recent years. Both groups offer the promise of novel therapies for various disorders such as diabetes, viral infections, HIV and cancer among others, according to Goverdhan Mehta and Senaiar Ramesh of the Indian Institute of Science, in Bangalore, writing in Chem Commun recently. Competitive and specific inhibition of glycosidase can be a common factor in developing new drugs for these wide-ranging disorders.
  As such, Mehta's team reasoned that the creation of analogues and structural variants of these two groups might lead to novel structures. They have synthesised and assessed the biological activities of a new family of polyhydroxylated polycyclic systems (polycyclitols). These compounds are all potential sugar mimics. The archetypal member of the group, a bicyclitol, can be thought of as a hybrid between two conduritols that share common ring junction carbon atoms. From a different perspective, he points out that the same molecule can be seen as a hybrid between two carbasugars which are ring annulated. Further modification of this archetype has led to various inhibitors of alpha-glucosidase, one of which is a particularly selective inhibitor.
  The molecule, an octahydroxydeca-hydronaphthalene, offers a good starting point for further testing against this and other enzymes involved in diabetes and viral disorders, says Mehta as this system is well poised for generating stereochemical and structural diversity as well as for combinatorial libraries. Additionally, the group has made several new structural isomers with carbocyclic ring size variation and their activities are being investigated.
  The researchers discuss their work in more detail in Chem Commun, 200, 2429-2430