Spray-dried nanoparticle formulation of efavirenz
Simon Collins,HIV i-Base
On the first day of the conference, researchers from the Council for Scientific and Industrial Research (CSIR) in South Africa (a scientific research institute primarily funded by the South African government), presented tentative results for the development of a nanoparticle formulation of the NNRTI efavirenz. [1, 2]
Nanotechnology has the potential to overturn many of the limitations to universal access:
- The quantity of active drug is greatly reduced perhaps by greater than 100-fold.
- Manufacturing costs have the potential to fall as dramatically, Most of the costs for generic drugs prices are due to raw materials: perhaps >90% compared to <1% of a Western drug price.
- Longer acting and delayed delivery formulations reduce the dosing period from daily to every 1, 2, 3 or 4 weeks etc. This should improve supply chain issues (fewer deliveries etc) and improve combination effectiveness and quality of life relating to adherence.
- Reducing the quantity of active drugs potentially reduces the risk of side effects,
many of which are dose-related. Compounds whose development has been stopped due to toxicity concerns, may become feasible at nanoparticle doses. For
example, another research group is even looking at transdermal indinavir. 
The group encapsulated efavirenz in polycaprolactone nanoparticles by a double emulsion spray drying technique using two organic solvents. The nanoparticles had an average size of 220.6 ± 0.950 nm when using ethyl acetate and 372.1 ± 19.96 nm using dichloromethane. This formulation overcomes the hydrophobic nature of efavirenz to improve bioavailability and met other manufacturing standards including encapsulation efficiency and a smooth particle surface.
If this research proves effective this has the potential to have as great an impact on global treatment as the first availability of generic antiretrovirals.
Human studies are needed before any idea of the dosing period can be determined. These are oral formulations and the group has already used thes same technique for AZT and d4T. They plan to develop fixed dose combination formulations. Results from in vivo studies (not yet started) are hoped to be
available by June 2011.
Although the reduced dosing is expected to reduce side effects, until this is determined, oral dosing with existing formulations prior to using a long-lasting version (in order to rule out hypersensitivity reactions) may be an important safety consideration, unless a rapid acting antidote to each drug is also available.
- Katata L et al. Spray dried PCL-efavirenz nanoparticles for improving the current HIV/AIDS treatment. Poster abstract MOPE0031. Link includes ePoster. http://pag.aids2010.org/Abstracts.aspx?AID=13785
- CSIR, Material Science and Manufacturing, Pretoria, South Africa http://www.csir.co.za
- Dubey V et al. Enhanced transdermal delivery of an anti-HIV agent via ethanolic liposomes. Nanomedicine, Volume 6, Issue 4, Pages 590-596 (August 2010). http://www.nanomedjournal.com/article/S1549-9634(10)00009-2/abstract
- Jain SK et al. Mannosylated gelatin nanoparticles bearing an anti-HIV drug didanosine for site-specific delivery. Nanomedicine, Volume 4, Issue 1,
Pages 41-48 (March 2008). http://www.nanomedjournal.com/article/S1549-9634(07)00251-1/abstract