PhD PCC/BIC

Employer
Wageningen University & Research
Location
Netherlands
Posted
September 12 2017
Discipline
Other
Position Type
Full Time
Organization Type
Academia

A PhD candidate for the project Coacervate protein carriers with application-dependent stability and delivery properties. Micelles composed of polyelectrolyte complexes (complex coacervate core micelles, C3Ms) are promising structures for protein protection and controlled delivery. They are simple to prepare: encapsulation of protein molecules can be achieved by mixing protein solutions with oppositely charged diblock copolymer solutions at stoichiometric charge ratio. The inner core of the C3M has a high loading capacity: many protein molecules can be incorporated into one micelle. Unfortunately, practical application is hampered by the low stability and high exchange dynamics of protein-containing C3Ms, due to the generally low charge density of protein molecules. In this project, we will take concrete steps towards application of C3Ms as protein carriers and delivery systems. We will use biocompatible block copolymers for encapsulation of two model proteins, i.e. the enzymes proline dehydrogenase and laccase, representative for a broad spectrum of enzyme types. Several strategies will be tested: 1) to enhance and tune the stability of the protein-polymer complexes, state-of-the-art bio-conjugation chemistry tools can be used to provide the enzymes with additional charged polypeptide sequences of variable length, and 2) crosslinking of the polyelectrolyte chains in the core can be used to inhibit protein exchange with the solution. The encapsulation efficiency, formation and decomposition kinetics, exchange dynamics (e.g., under physiological solutions) and the effect of packaging on the activity of the enzymes will be determined. Finally, we will explore a number of release mechanisms. On the basis of the obtained results, it will be possible to design C3M protein carriers of which the stability and dynamics are tuned to specific applications.



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