Contact

Laboratory for General Biochemistry and Physical Pharmacy
Ghent University
Ottergemsesteenweg 460
9000 Gent
Belgium
Tel: 0032 9 264 80 47 (secretary)
Tel: 0032 9 264 80 74 (direct)
Fax: 0032 9 2648189
E-mail: Pieterjan.Merckx@ugent.be

Biography

Pieterjan graduated from the Ghent University as a MSc Drug Development – Pharmacist in 2015. His master’s thesis, entitled ‘Synthesis, physicochemical characterisation and cytotoxicity evaluation of different PGA-PTX conjugates’ was performed at the Polymer Therapeutics Laboratory, part of the Centro de Investigación Príncipe Felipe, Valencia. After obtaining his master’s degree, he started his PhD at the Ghent Research Group on Nanomedicines (GRGN) as a doctoral fellow of the Agency for Innovation by Science and Technology (IWT Vlaanderen).

Research interests

Nanomedicines, RNA interference, siRNA, pulmonary delivery, nanogels, hybrid nanoparticles, pulmonary surfactant, nebulization, dry powder inhalation

Summary of Research Project(s)

RNA interference (RNAi) is widely regarded as one of the most revolutionary concepts in molecular biology and medicine. The intracellular RNAi pathway is typically activated by small ribonucleic acid effectors such as small interfering RNA (siRNA), which hereby induce sequence-specific gene silencing on the post-transcriptional level. In this way, the mechanism allows for highly specific targeting of virtually any disease-causing protein, enabling a consistent knockdown that can last for days up to weeks. The application of RNAi in a therapeutic context is therefore considered as superior to today’s medicines in terms of efficacy and toxicity.

The lung is found to be an attractive target tissue for siRNA therapeutics, since local administration enables direct delivery to target cells for pulmonary disease. Hence, systemic exposure is avoided and drug retention is prolonged, leading to reduced toxicity and side effects combined with an increased efficacy of a single siRNA dose. However, the main bottleneck towards clinical translation of pulmonary siRNA therapeutics is intracellular delivery, which requires guidance by a safe and effective nanoparticle to overcome the many extra- and intracellular barriers encountered upon administration.

To this end, we aim to design a bio-inspired nanocomposite, optimized for pulmonary siRNA delivery. The proposed carrier merges the benefits of a biodegradable, controlled release dextran-based nanogel core, which has a high loading capacity for siRNA, with a lipid-protein bilayer coating based on the composition of pulmonary surfactant. The latter provides for an enhanced biocompatibility and stability, combined with the recent finding that a pulmonary surfactant-based coating enhances cellular siRNA delivery, which was already reported by our group. More specifically, the particle will be designed and optimized in terms of biocompatibility and efficacy in pulmonary disease related target cells and stability in the lung extracellular matrix. In addition, the stability upon nebulization and spray drying will be assessed. The final goal is to develop a broadly applicable nanoparticle platform for pulmonary siRNA delivery with maximal efficacy and biocompatibility, which will be evaluated in an in vivo mouse model for severe refractory asthma as a first step.