Nanoparticles deliver improved antifungal activity

Submitted by Aspergillus Administrator on 26 October 2010

The hydrophobic nature of many antifungal drugs is problematical for effective drug delivery and absorption in patients.
Considerable research on a drug delivery system based on bio-degradable polymers has been productive in identifying suitable carriers such as the thermoplastic polyesters eg poly(lactide-co-glycolide), which exhibit good biocompatibility and biodegradability alongside mechanical strength. These bio-degradable polymers have been developed into a new type of drug delivery system called nanoparticles – which can be used to deliver a wide range of drug classes including anti cancer drugs, antihypertensive agents and various peptides, proteins, and vaccines.
Last month a publication by Patel et al describes the development of nanoparticles loaded with the hydrophobic antifungal drug – itraconazole.
The particles were characterised for morphology and also for their ability to inhibit growth of Aspergillus flavus. The itraconazole loaded nanoparticles achieved an inhibition of A. flavus growth for an 11 day period at a concentration of 0.03mg/ml or rather 1/100th of the concentration of itraconazole alone (in emulsified form). It is envisioned that the use of nanoparticles loaded with itraconazole increases its bioavailability by improving its dispersion in water and greatly enhances its antifungal activity.
These results are promising for a significant improvement in the delivery of antifungal drugs and hence their efficiency, but more in vivo studies will help to advance this technology.

Another advantage of the nanoparticle technology which will hopefully prove fruitful, is targeting specific organ delivery.
For example the blood brain barrier precludes the transport of many drugs to the brain. However Chen et al published data in June this year that an itraconazole loaded nanoparticle with a special tag on it derived from the rabies virus, allowed transport of the itraconazole into the brain when compared to nanoparticles without the rabies derived tag. The potential for targeting intracranial fungal infections in this way is exciting.

From the perspective of delivering targeted treatment to lung infections -a special type of nanoparticle that penetrates mucus – was reviewed by Lai et al last year. If a nanoparticle/antifungal drug can be developed which avoids the normal rapid mucus clearance mechanisms, the prospect of delivering antifungal drugs right to the site of infection should greatly improve the chances of effective treatment. This approach would be particularly useful for cystic fibrosis patients too.