Thus the necessary tablet, capsule or syrup is obtained. But what would happen if biodegradable materials were used instead of these neutral excipients? This was already possible with some active substances, and can now be applied to many others! The team led by Didier Bourissou in the Laboratory for Fundamental and Applied Heterochemistry (CNRS/University Toulouse 3), has indeed managed to develop a novel synthetic process for these materials which significantly increases their diversity.
Some biodegradable polymers such as polyesters have already been employed as excipients in pharmacology. But this was only possible when they were mixed with certain active substances such as anticancer drugs or growth hormones. And in the field of surgery, the secret of absorbable sutures does indeed reside in the use of these same polyesters.
What are the principles underlying these "new generation" drugs? The biodegradable excipient containing the active substance can take the form of an implant – a 1 cm-long rod about one millimetre in diameter – which is inserted just under the skin. This procedure is performed by a doctor and only takes a few minutes. The specificity of these polyesters is that they can be hydrolyzed; in other words, broken down by water, which is unlucky for them, as our bodies are full of this substance. Thus the excipient gradually breaks down, over a week, a month or three months, depending on its type, releasing the active substance it contains. Hence the major advantage of the technique: biodegradable excipients enable the controlled administration of sustained-release drugs. This is of considerable benefit in the setting of chronic diseases, as it avoids frequent, repeated intakes of medicines. Another positive point is that this method reduces side effects; by circumventing the digestive tract, the active substance passes directly into the bloodstream. Thus it is also possible to reduce the quantity of drug administered, as there is no longer any need to allow for its partial destruction as it passes through the digestive tract.
In view of these advantages, why can the technique not be extended to a broader range of active substances? Because, until now, we only knew how to make these biodegradable polymers using two monomers (the basic components of polymers), lactide and glycolide. It is rather like making a bead necklace when only green and red beads are available. And in the same way that such a two-coloured necklace would not match all outfits, so the polyesters obtained cannot be combined with just any active substance. Without accounting for the fact that when using these little reactive lactide and glycolide monomers, industrial preparation of the polymers requires lengthy reaction times at high temperatures (e.g. several hours at 140°C-160°C).
This is where Didier Bourissou's team same up with the idea of changing the recipe and ingredients in order to facilitate access to these polyesters and increase their diversity. Many tests later, they achieved their goal. In collaboration with Isochem, they have developed a new synthetic process for these polymers. This involves new elementary building blocks, the O-carboxy anhydrides, which are much more reactive (i.e. more beads for our necklace), so that the polyesters can be prepared under much less harsh laboratory conditions (e.g. a few minutes at 25°C). And above all, a much wider variety of polymers is available, thus multiplying the chances that an active substance will find its appropriate biodegradable excipient. These promising results have given rise to the filing of two patents.
An unquestioned advance in the daily routine of patients, this technique might also be popular with the major pharmaceutical companies, as it would constitute an added-value for traditional drugs which could be presented in a sustained-release formulation.
Monica McCarthy | EurekAlert!
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