Prof. Dr. Scott McNeil - Nanopharmaceutical & Regulatory Science Group

The Nanopharmaceutical & Regulatory Science (NPRS) group investigates important topics in nanopharmaceuticals and their related regulatory aspects and challenges. We develop and characterize novel nano-based formulations to improve the therapeutic index of active pharmaceutical ingredients. In collaboration with other research institutions, we identify and investigate critical quality attributes of nanopharmaceuticals and nanosimilars, such as mechanisms of action, safety, and practical application issues. We also interface with the pharmaceutical industry and regulatory authorities to establish science-based guidelines on the safe and correct use of nanopharmaceuticals and nanosimilars.

We offer master's thesis projects for students interested in nanotechnology-based formulations and the delivery of peptides and proteins. Our lab's expertise covers different areas, such as the design and manufacturing of targeting ligands and nanoparticles, process optimization, physicochemical characterization, particle stability, applied studies where the uptake of nanoparticles is evaluated in relevant cellular models, and transcytosis studies using human induced pluripotent stem cells (hIPSCs) to assess the nanoparticle's ability to cross the blood-brain barrier (BBB).

Student projects typically involve nanoparticle production and purification, detailed physicochemical characterization, methods development, and cellular and molecular biology approaches. In addition to working on exciting research projects, students will receive comprehensive training in all aspects of research work, including reviewing current literature, project planning, designing experiments, lab work, data evaluation, and science communication.

To apply for a position in our lab, interested students should contact us as early as possible. Please apply or ask questions by emailing scott.mcneil@clutterunibas.ch or come to our lab and talk directly to us!

Available Projects

Project 1: Development of Targeted Anti-Cancer Drug Nanoformulations and Investigation of their Therapeutic Potential

Cancer remains a primary global health concern, and the search for more effective and precise treatment options is an ongoing challenge. This project aims to explore a cutting-edge approach in cancer therapy by developing targeted anti-cancer drug nanoformulations. These nanoformulations involve encapsulating anti-cancer drugs in nanoscale carriers, which can be engineered for site-specific drug delivery.

This project will focus on designing and synthesizing lipid-based nanocarriers and encapsulating anti-cancer drugs. The student will work on optimizing the drug-loading capacity and stability of these carriers and explore carbohydrate-based targeting strategies to ensure the selective delivery of these nanoformulations to cancer cells while minimizing damage to healthy tissues. The student will perform cell culture experiments to evaluate the drug's ability to inhibit cancer cell growth and induce cell death.

They will learn how to analyze the experimental data to determine the efficacy of the developed nanoformulations compared to traditional drug delivery methods and interpret the findings to identify potential improvements and challenges.

Project 2: Design and Synthesis of Next-Generation Carbohydrate Clusters and their Application as Receptor Ligands for Targeted Delivery of Lipid Nanoparticles

This student project aims to explore a novel avenue in drug delivery by focusing on the design and synthesis of next-generation carbohydrate clusters that can serve as receptor ligands for targeted delivery of lipid nanoparticles. By harnessing the specific interactions between carbohydrates and cellular receptors, this project seeks to enhance the precision and efficiency of drug delivery systems.

The project will involve the design of carbohydrate clusters with specific patterns and arrangements. These clusters will be tailored to engage with receptors on target cells and explore the avidity of the ligand-receptor interaction. The student will synthesize carbohydrate clusters, utilizing organic chemistry techniques to create well-defined and pure compounds. The synthesis process will include preparing various carbohydrate building blocks and their assembly into clusters.

The student will develop lipid nanoparticles that encapsulate sample therapeutic compounds and optimize the formulation to provide stable and efficient drug delivery vehicles. They will investigate the binding affinity and specificity of the carbohydrate-decorated lipid nanoparticles to target cells utilizing cell culture experiments and molecular biology techniques to assess the effectiveness of receptor targeting. The student will evaluate the internalization of the lipid nanoparticles and their payload into target cells and asses a potential advantage of the ligand clustering approach. They will measure the efficiency of drug delivery and assess any changes in cellular response.

The student will learn how to analyze the experimental data to determine the efficacy of the developed targeted nanoformulations compared to traditional drug delivery methods and interpret the findings to identify potential improvements and challenges.

Project 3: Development of Biomimetic Protein-Phospholipid Conjugates and Investigation of Their Application Potential in Enzyme Encapsulation

This student project aims to explore the development of biomimetic protein-phospholipid conjugates and investigate their potential applications in enzyme encapsulation. Students in this project will explore innovative methods for delivering and protecting enzymes for various biotechnological applications by mimicking the natural processes within cells.

The student will be responsible for designing and engineering protein-phospholipid conjugates. These conjugates will combine the lipid affinity for phospholipid membranes with the functionality of specific proteins attached to the lipid component. The student will develop conjugation techniques to attach proteins to phospholipid bilayers. This may involve covalent bonding, non-covalent interactions, or other strategies to ensure stable associations. They will take advantage of the high lipid affinity of obtained products and incorporate them into the lipid nanoparticle structures.

The student will employ advanced characterization techniques to analyze the physicochemical properties of the obtained lipid nanoparticles and determine enzyme loading capacity. The project will include investigating the enzymatic activity of the encapsulated enzymes. This involves in vitro experiments to assess the stability and functionality of enzymes within the conjugate.

The student will learn how to analyze the experimental data to determine the efficacy and applicability of developed enzyme encapsulation approaches and interpret the findings to identify potential improvements and challenges.

Project 4: Design and Development of Polysaccharide-Based Nanoparticle Systems for Drug Delivery to the Brain

 This student project focuses on designing and developing advanced drug-delivery systems for delivering therapeutic agents to the brain. The central challenge in brain drug delivery is overcoming the blood-brain barrier (BBB), which restricts the entry of most drugs. Polysaccharide-based nanoparticles offer a promising solution by facilitating targeted and controlled drug release within the brain.

The project will involve the design of polysaccharide-based nanoparticles as drug carriers. The student will consider factors such as particle size, surface charge, and functionalization to enhance BBB penetration. They will explore various natural and synthetic polysaccharides and select the most suitable candidates for nanoparticle development. The work will involve the optimization of the nanoparticle manufacturing process. The student used our in vitro models from hIPSCs of the BBB to assess the ability of the nanoparticles to cross this barrier and reach brain cells. The student will examine the biocompatibility and safety of the developed nanoparticles. Cytotoxicity and biocompatibility studies will be conducted to ensure minimal harm to brain tissues.

The student will learn how to analyze the experimental data to determine the efficacy and applicability of developed enzyme encapsulation approaches and interpret the findings to identify potential improvements and challenges.

Project 5: Uptake and transcytosis of nanoparticles in relevant cell models

This project aims to determine the efficiency of different nanoparticles' uptake in relevant cellular models for specific diseases. For instance, we will test nanoformulations encapsulating anti-cancer drugs in cancer cells. The specific objective is to identify which nanoformulation can be taken up more efficiently and achieve an efficient drug release mechanism while also identifying potential cellular signaling pathways.

On the other hand, the central challenge in drug delivery to the brain and CNS is overcoming the BBB, which restricts the entry of most drugs. We have established a human model for BBB derived from hIPSCs. Polysaccharide-based nanoparticles offer a promising solution by facilitating targeted and controlled drug release within the brain.

This project will test polysaccharide-based nanoparticles as drug carriers for BBB models, including transcytosis experiments and uptake in acceptor cells. This may include anti-cancer drugs or lysosomal enzymes for enzymatic replacement therapy. The project will involve nanoparticle formulation, characterization, and cell biology studies.

The student involved in this project will gain experience in planning and analyzing experimental data to determine the efficiency of various nanoformulations in the relevant models.