Nano-Formulation and Drug Delivery

Light scattering and field-flow fractionation provide characterization capabilities essential in developing novel nano-formulations, whether RNA-bearing lipid nanoparticles, drug-carrying liposome, or other carrier vehicles like PLGA micelles.

Basic sizing of nano-formulated particles is usually carried out initially in a batch (unfractionated) dynamic light scattering (DLS) instrument which makes measurements in a microcuvette, such as a DynaPro NanoStar or ZetaStar. Far more accurate size distributions are obtained using a separation step e.g. SEC-MALS for particles up to ~ 100 nm in size or SEC-MALS for particles up to 1000 nm in size. Both of these techniques are sensitive enough to resolve particles that differ by just a few nm in radius, amongst a heterogeneous distribution.

One of the most important analytical challenges in nano-formulation development is the determination of whether a drug, therapeutic peptide or nucleic acid is incorporated into the carrier, bound to the outside or free of the carrier. The combination of SEC or FFF with a DAWN MALS detector and WyattQELS online DLS module can help answer these questions by identifying the particle's conformation and content as a function of size, and also detecting and identifying unbound molecules.

For stable formulations, nano-formulated constructs may be evaluated in dozens or even hundreds of conditions in the DynaPro Plate Reader to minimize aggregation. The ZetaStar is ideal for measuring the zeta potential of drug-delivery nanoparticles in a series of formulation buffers, automated by an autosampler, as well as high-salt buffers that disrupt conventional zeta potential measurements when bubbles are formed at the electrodes by electrolysis. Zeta potential is an excellent indicator of the N/P ratios well as colloidal stability.