Hi Vaideesh.

The short answer to your question is.........................it depends.

It depends on a variety of factors that include, but are not limited to;

1) the stability of your suspension - how likely is it to aggregate (see below) or how stable are your biodegradable NPs.

2) the tendency of the NPs to aggregate in suspension NOTE: post nebulisation, you will see some aggregation-like interactions between the NPs, however, this may well not be aggregation but close physical proximity as multiple NPs are encapsulated in a very single small aqueous droplet and when they deposit on a surface, they tend not to spread as the droplet volume is so small that it does not allow it.

3) the type of nebuliser you are going to use - active vibrating mesh is likely the one Kent Sci refer to and I attach some papers below that might be of interest. Assuming that your NPs dont aggregate to form big clumps, you should be fine with respect to clogging, the apertures in the mesh are in the order of 3-4microns in diameter, and they de-clog themselves readily. DISCLAIMER: I work for an active vibrating mesh company, and quite possibly the one Kent Sci is offering to you. 

Jet (compressed air) nebulisers in my experience are not suitable for NP delivery. There is significant shear force exerted on the suspended NPs and any conjugates may come off, or encapsulating features may be disrupted. They are not recommended for any type of suspension, micron or nano scale. 

Passive (i.e. not actively vibrating) mesh nebulisers may well clog if the NPs aggregate. Like jet nebulisers they are also not recommended for any type of suspension.

4) the formulation excipients/buffer - high viscosity or low surface tension may affect the ultimate droplet size.

You ask what might be the ultimate droplet size. Again I am afraid that that depends. It depends on the droplet size generated by the nebuliser itself, coupled with the physico-chemical properties (surface tension and viscosity) of your formulation.

I also should make you aware, that "what droplet size"you record will be predominately be dictated by the equipment that you use to characterise it, e.g. laser diffraction, Andersen impactor at 28.3LPM, NGI @15LPM, Marple 298 @ 2LPM. Which ever you choose to use............stick with it.

If you are concerned about what droplet size is produced, do not get too concerned until you reach large animal/human testing phase. Very little aerosol will be delivered to mice and rats for example, you are likely to have to instill in the mice. Rats can be used for aerosol studies (see paper below). Also, don't get too hung up on the classic "only droplets less than 5 micron can be inhaled".........droplets over 5 microns can also reach the periphery of the lung if you use the right nebuliser.

As with most things of this nature, I suggest you go ahead and try it. There is sufficient literature out there that gives confidence that a variety of NP suspensions can be effectively aerosolised, the papers below are 2 such examples.

Finally, in making your choice of nebuliser, I encourage you to consider your ultimate target patient. All going well, this formulation will be provide therapeutic utility and will be submitted for regulatory approval. Their key concern beyond safety/toxicity of the NPs, is the reliability and reproducibility of dosing. Different nebuliser systems will deliver different amounts to the lungs, and to different regions within the lungs and so you need to consider that also. I have plenty of comparative studies on my profile if you wish to get an idea of the differences in delivered dose in some setups.

I hope you find this answer of use. Best regards,

Ronan.

Article Optimized Aerosol Delivery to a Mechanically Ventilated Rodent

Article Magnetic core-shell nanoparticles for drug delivery by nebulization

Article Early-Stage Development of Novel Cyclodextrin-siRNA Nanocomp...

Thank you for the answer. It is very informative and the articles attached are very resourceful too.