Alessandro Corona

The effect of oil type on the aggregation stability of nanostructured lipid carriers.

Second generation lipid systems for the delivery of bioactive compounds have been developed by mixing a liquid carrier oil with a solid lipid to form so-called nanostructured lipid carriers (NLCs). In this study, we investigated the effect of different liquid carrier oils on the crystallization and aggregation behavior of tristearin NLC dispersions. We found that NLC suspension stability was strongly affected by the type and amount of the carrier oil. As the oil concentration was increased, the crystallization and melting temperatures decreased, the polymorphic transformation rate increased, the particles became more spherical, and suspension stability was enhanced. These results suggest that oil trapped within the growing crystal matrix accelerated polymorphic transformation but retarded the large shape change normally associated with the transformation. We also found that considerably less surfactant was necessary to produce stable NLC suspensions than was required to stabilize solid lipid nanoparticle (SLN) suspensions without a carrier oil. Based on preliminary simulation results, we hypothesized that improved NLC suspension stability was attributable to both reduced particle shape change, which created less new surface area to be covered by surfactant, and increased mobility of surfactant molecules, which resulted in available surfactant being more efficient at covering created surface area.

Experimental investigation and population balance equation modeling of solid lipid nanoparticle aggregation dynamics

Solid lipid nanoparticles (SLNs) have applications in drug delivery and the encapsulation of bioactive, lipophilic compounds. However, SLNs tend to aggregate when stored due to the lipid crystals undergoing a polymorphic transformation from the unstable α form to the stable β form. We developed a population balance equation (PBE) model for prediction of average polymorph content and aggregate size distribution to better understand this undesirable behavior. Experiments with SLNs stored at room temperature showed that polymorphic transformation was the rate determining step for our system, SLNs with smaller initial size distributions aggregated more rapidly, and aggregates contained particles with both α and β crystals. Using parameter values estimated from our data, the PBE model was able to capture the bimodal nature of aggregate size distributions, the α-to-β polymorph ratio, and the faster aggregation dynamics of SLNs with smaller initial size distributions. However, the model was unable to adequately capture the fast disappearance rate of primary particles, the broad size distributions of formed aggregates, and the significant α content of aggregating particles. These discrepancies suggest that a PBE model which accounts for polymorph content as an internal variable along with aggregate size may be required to better reproduce experimental observations.