See 2018

Modular single-chain polymer nanoparticles in drug delivery

In this thesis synthesizing strategies were employed, in intramolecular crosslinking of thiol polymers, to yield a variety of single-chain polymer nanoparticles (SCNPs).

Drug delivery

‘These nanoparticles are around 10 nm, in size,’ says Pia Kröger. ‘This is markedly smaller than conventional polymer nanoparticles, above 100 nm. We investigated if such nanoparticles would go into the brain and can henceforth serve as a delivery agent in Alzheimers Disease. We studied its biodistribution behaviour. Two main strategies for drug delivery exist – coupling and encapsulation – for example to facilitate drug delivery in entering brain cells.’

All of the obtained nanoparticles were water-soluble, and in the last year Pia focused on nanoparticles soluble in organic solvents. ‘Enabling post-formation modification with a range of amines was a decisive next step,’ Pia says. ‘Also fluorescent labels and alkyne moieties for click conjugation were conjugated. We succeeded in coupling peptides and in treating the single-strain particles to mimick regular protein behaviour. This is a decisive feature for designing potentially new drug delivery strategies.’

Further, the potential of drug encapsulation was demonstrated by incorporation of the solvatochromic dye Nile red into glycol-SCNPs. Shifts in the fluorescence spectra of Nile red confirmed dye encapsulation. ‘Encapsulation and release studies of the antibiotic Rifampicin revealed controlled release over 24 h,’ Pia says. ‘Accordingly, the SCNPs may be utilized as drug carriers. Alternatively, drugs may be conjugated to the SCNPs.’

The thesis project of Pia, working in the Biomolecular Nanotechnology Group, was part of a ZonMW project in which also a blood-brain barrier (BBB) model was produced and described.

‘This is an necessary step in order to evaluate the biological effect of nanoparticles prior to animal studies,’ Pia explains. ‘The model has to be worked on further still, in order to serve as a suitable analysis of transcellular passage activity of these SCNPs. Only then the full potential of SNCPs can be determined.’

Collaborations

Within the ZonMW project three other PhD students, post-docs and several companies were involved. ‘We had frequent half yearly meetings,’ Pia says.

‘Also I collaborated with five master students which I supervised on various aspects of my research. It decisively changed my perspective as to my future job. I very much liked supervising and thinking strategically on this kind of composite and complex projects.’

Future career

After a post-doc here in Twente - which will last a few months, to complete some extra aspects of this thesis work, and beyond – I would like to introduce my academic skills in industry, for example working as a project manager in a bigger company in which different groups are housed, preferably in polymer science.’

‘Using my managerial skills, I believe I can accompany these groups in joint multidisciplinary projects. I don’t think many lab hours will be involved in this future job, which is a bit of a shame. However, it would be nice if planning experiments within the lab will be part of the future job. In this way I can be involved in research in an active manner.’