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New Opportunities for Nanoparticles Through Nasal Delivery

Having gathered momentum for decades, nanoparticles (NPs) reached a critical new phase in their evolution during the pandemic, with both the Pfizer/BioNTech and Moderna mRNA vaccines employing this approach to protect millions across the world against Covid-19.

We speak to Dr. Irene Rossi and Dr. Eleanor Canipa at Nanopharm, about this emerging market and insights into the development process.

Q: What are the advantages of nanoparticle systems?

A: The growing focus on nanoparticle systems has been driven by the various benefits they offer as a carrier for therapeutic agents, and particularly biologics such as nucleic-acid-based therapies. Here, nanoparticle encapsulation provides biologics with a stable platform to cross multiple biological barriers and support effective uptake within target cells, whereas without encapsulation, some biologics can degrade quickly. Specific advantages of nanoparticle systems include their high level of encapsulation efficiency; the fact that the molecule is protected against enzymatic degradation; their inherent adjuvant properties, which result in increased immunogenicity for RNA and DNA vaccines; and the improved pharmacokinetic profile they can deliver by avoiding renal excretion and clearance via the mononuclear phagocyte system (MPS).

Compared with viral vectors, nanoparticle systems support a reduced immune response, mitigating the risk of the therapy triggering an adverse effect. They offer other benefits too, including low toxicity and the potential to deliver large payloads with a controlled, sustained release.

Q: How are nanoparticle systems formulated?

A: Nanoparticles can be formulated using several methods, the foremost being to dissolve lipids (which are mixed with a nucleic[1]acid solution) in ethanol to produce lipid nanoparticles (LNPs) via self-assembly. Alternatively, microfluidic mixing processes have been designed to achieve rapid and controlled folding of fluids within microseconds to milliseconds for precise control of particle size, more homogeneous size distribution, higher encapsulation efficiency, and greater reproducibility than bulk methods. An example of this approach is hydrodynamic flow focusing, a microfluidic laminar flow method where particles are formed at the interface of laminar flow streams. However, this process is limited in throughput (< 10mL/h) and is mainly used for preparing liposomes, which have less structural complexity than LNPs.

Another rapid-mixing process is ‘Tjunction mixing’, where turbulent mixing in a macroscopic channel (> 1mm) can achieve small nanoparticle sizes (< 100nm), but this method cannot scale down to the small volumes (μL) needed for high-throughput library screening of nanomaterials.2

For each method, particle size – and the ability to control it – is an important parameter as it greatly influences the fate of the nanoparticle in vivo. Bulk processes, namely self-assembly, do not require specialised equipment, but they lack precise control over mixing time and thus create large (> 100 nm), polydisperse particles with low encapsulation efficiency that vary from batch-to-batch and can require more downstream processing in large-scale manufacturing. This reduces yields and increases production costs.