Universiteit Leiden

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Research project

Polypept(o)ide-based Cylindrical Polymer Brushes as Multifunctional Drug Delivery Systems

The polypept(o)ide hybrid material attracted more and more attention over the past decade by combining the multifunctional characteristics of polypeptides with the shielding characteristics of polypeptoid-pSar possessing similar properties as a shielding material as polvethylene glycol(PEG). Polysarcosine can be synthesized in multiple ways e.g. solid phase peptide synthesis, polycondensation and nucleophilic ring-opening polymerization (ROP) of a-amino acid N-carboxyanhydrides (NCAs) and N-substituted N-carboxyanhydrides(NNCAs).

Bonan Zhao

Barz and coworkers established the synthesis of homopolypeptides and -peptoids as well as hetero co polypept(o)ides up to triblock structures by sequential NCA polymerization under non-glovebox conditions. Moreover, this method is suited for the synthesis of cylindrical polymerbrushes. This term for the otherwise called bottlebrushes or molecular brushes was introduced by Wintermantel et al. in 1996. These brushes are composed of many polymeric side chains grafted onto a linear polymeric backbone. By variation of the chain length of the backbone and/or the sidechains as well as the grafting density of the sidechains onto the backbone it is possible to control the shape and other characteristics of these kinds of polymerbrushes precisely. 

PhD Workplan

During my PhD thesis, I plan to synthesize and characterize the modified graft copolymers polylysine-g-polysarcosine(pLys-g-pSar) and its conjugates with the aim to precise tailor, control and understand these systems and their structure-property relationships. Additionally, my thesis focuses on designing nanoparticles with shell-core structure for drug encapsulation and with patterned backbones to deploy the surface structure-dependent properties of these particles. Due to its interdisciplinary character based on organic synthesis, polymer chemistry, physical chemistry and medicine, this proposal is divided into two parts. Part one focuses on Particle Synthesis and Characterization to derive a fundamental understanding of controlled synthesis, structure-property relationships and morphology effects. The second aspect of Medical Application is dedicated to the investigation of the biological components attached to the carrier systems and the associated therapeutic responses.

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