Case study – Doxil®
SPARTA® analysis of liposomal formulation of doxorubicin
When formulating a nanomedicine for drug delivery, a key design factor is loading the nanoparticle carriers with cargo, ranging from small molecule drugs in liposomes to nucleic acids in LNPs. Current prevalent methods to assess carrier loading rely on bulk measurements, which typically requires particle lysis and quantification of the amount of cargo released using HPLC, for example.
SPARTA® provides a revolutionary new approach to assessing nanoparticle loading on a single particle basis where cargo loading can be directly identified and quantified without the need for sample modification. This not only strongly facilitates development workflows, but also provides a fundamental increase in analytical detail as particle-to-particle loading heterogeneity can be determined. In addition, SPARTA® can simultaneously capture size measurements to evaluate a formulation’s size-loading characteristics. This information is of crucial importance for optimising R&D and production processes to achieve homogeneous, reliable and safe formulations with predictable performance.
SPARTA® was used to measure Doxil® loading in individual liposomes. An average drug loading of 2.8 x 10-14 mg doxorubicin per liposome was observed, with significant variation in loading identified. Seemingly empty or very poorly loaded liposomes were detected, as were very highly loaded liposomes.
By simultaneously measuring the size variation of individual liposomes, drug distribution relative to particle size can be visualised. The majority (80%) of liposomes fall within the shaded area, where loading does not significantly increase with size. Significant outliers were detected with extreme loading and larger increases in particle size.
Penders J. Stevens M.M. et al. In preparation
This work is carried out in collaboration with the Nanotechnology Characterization Laboratory (NCL) at the National Cancer Institute (NCI) U.S. who kindly provided the samples for this study.
