SinS - Abstract

Abstract Information :

Nanomedicine has the potential to revolutionise both diagnostics and therapeutics. Whilst nanoparticles as drug delivery systems ( are slowly transitioning into clinic, regulatory governance of these formulations is still controversial. controversial. Highly specific frameworks include guidelines for medicinal polymeric nanocarriers encompassing contemporary understanding yet fundamental issues are still emerging, including defining if a nanocarrier is an active ingredient or excipient. This h ighlight s that there is still much uncertainty for the field and a s a result the translation rate m ay slow furthe r. A way to circumvent these potential issues is to develop robust in vitro characterisation profiles with advanced biological analyses. Here, we investigate both physicochemical and biological methodologies for nanoparticle applications , evaluat ing the pertine nce of the methodology and the performance of the material .

Given the unique quantum behaviours of materials in the nano range, we considered the impact on compatibility with size measuring techniques, comparing optical (DLS, AF 4 and imag e based (SEM,TEM) applications for characterisation of polymer nanoparticles P articles were shown to be distinct sizes spanning 30 180nm . For the biological analyses, EMA guidelines stipulate to cytotoxic assays and NP internalisation in basic monolayer cell cu ltures . Further, NPs were investigated for the capacity for ROS production traditionally conducted with metallic particles , and in clud ed spheroid cultures for a microtissue/ microtumour model s for cytotoxicity and tissue penetration.

The results o f the spheroid internalisat ion work refined our polymer library down to three top candidates . Finally, prior to in vivo validation of the NPs, ex vivo immunogenicity evaluations using healthy human blood was conducted to investigate the potential for serious adverse immune responses as well as haemolysis. The results of which were all negative and candidates proceeded to a small cohort murine study to e valuate single dose toxicity and biodistribution of NPs. All NPs were shown to be promising DDS in vivo , were fully compatible and were shown to accumulate in the tumour as early as 1 h post administration.

Through extensive characterisations we have been able to refine NP candidates further than standard practices . These candidates, thus the characterisation pipeline, was validated following in vivo assessments.