Molecular Design of Squalene/Squalane Countertypes via the Controlled Oligomerization of Isoprene and Evaluation of Vaccine Adjuvant Applications.

The potential to replace shark-derived squalene in vaccine adjuvant applications with synthetic squalene/poly(isoprene) oligomers, synthesized by the controlled oligomerization of isoprene is demonstrated. Following on from our previous work regarding the synthesis of poly(isoprene) oligomers, we demonstrate the ability to tune the molecular weight of the synthetic poly(isoprene) material beyond that of natural squalene, while retaining a final backbone structure that contained a minimum of 75% of 1,4 addition product and an acceptable polydispersity. The synthesis was successfully scaled from the 2 g to the 40 g scale both in the bulk (i.e., solvent free) and with the aid of additional solvent by utilizing catalytic chain transfer polymerization (CCTP) as the control method, such that the target molecular weight, acceptable dispersity levels, and the desired level of 1,4 addition in the backbone structure and an acceptable yield (∼60%) are achieved. Moreover, the stability and in vitro bioactivity of nanoemulsion adjuvant formulations manufactured with the synthetic poly(isoprene) material are evaluated in comparison to emulsions made with shark-derived squalene. Emulsions containing the synthetic poly(isoprene) achieved smaller particle size and equivalent or enhanced bioactivity (stimulation of cytokine production in human whole blood) compared to corresponding shark squalene emulsions. However, as opposed to the shark squalene-based emulsions, the poly(isoprene) emulsions demonstrated reduced long-term size stability and induced hemolysis at high concentrations. Finally, we demonstrate that the synthetic oligomeric poly(isoprene) material could successfully be hydrogenated such that >95% of the double bonds were successfully removed to give a representative poly(isoprene)-derived squalane mimic.

Transport and encapsulation of gold nanoparticles in carbon nanotubes.

Nanoparticles confined in small volumes exhibit functional properties different from that of the bulk material. Furthermore, the smaller the volume available then the greater the effects of confinement are observed to be. Metallic nanoparticles encapsulated within carbon nanotubes have been proposed for many applications ranging from catalysis to quantum storage devices. In this study we examine encapsulation of discrete gold nanoparticles (AuNP) within multi-wall carbon nanotubes (MWNT), with internal diameter less than 10 nm. During the encapsulation process AuNP undergo Ostwald ripening allowing them to reach a diameter that precisely matches the internal diameter of MWNT (snug fit). The use of supercritical CO2 as a processing medium enables efficient transport and irreversible encapsulation of AuNP into narrow nanotubes. Once inside MWNT, the nanoparticles are unable to grow further and retain their spheroidal shape. This dynamic behaviour observed for AuNP differs significantly from the behaviour of molecular guest-species under similar conditions.