Bottom-up Approach
The most common nanoparticle formulation method relies on the fast mixing of two miscible phases (lipids/polymers in an organic solvent and aqueous buffer), leading to a drop in solubility of the lipids/polymers, which start to agglomerate to form nanoparticles. Commonly known as nanoprecipitation/self-assembly process.
Mixing speed affects the nanoparticle size - faster mixing produces smaller particles. Also, the more efficient and homogeneous the mixing is, the better the control over the size and distribution.
Microfluidic chip-based platforms can maintain the fluid flow in laminar conditions, and provide optimal control of the final nanoparticle physicochemical parameters.
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Benefits:
- Fast processing time
- Low volume range µL to mL
- Size control & repeatability
- PDI <0.2 & EE >95%
Top Down Approach
The phospholipid, carrier oil and any hydrophobic actives are dissolved in a solvent, which is subsequently removed via evaporation. A buffer is added to the resulting precipitate and then warmed and vortexed to hydrate the phospholipids.
The antigen (or other hydrophilic actives) are added to the solution whereupon large multi-layer vesicles (MLVs) are generated.
These MLVs are then processed through a Microfluidizer® processor to reduce their size to small uni-lamellar vesicles.
Benefits:
- Scalability with repeatability
- Higher volume range mL to L
- Good size control
- GMP level equipment
