A novel top-down approach to produce super small drug nanocrystals to target intracellular organelles

About the Project

Would you like to join a highly dynamic, international research group to develop super small drug nanocrystals (NCs)? In this project, you will develop drug NCs of ~100 nm to target intracellular organelles. In comparison to other nanoparticle-based drug delivery systems, such as liposomes and other lipid- and polymer-based nanocarriers, NCs have a series of unique advantages: 1- They can be produced using highly scalable technologies, 2- There is no need for organic solvents or extreme pH during manufacture, 3- They have long term stability, opposite to NPs made of soft materials such as lipids or polymers, 4- NCs sterilisation is feasible allowing parenteral administration, 5- Their carrier-free nature affords the chance of avoiding the use of toxic excipients, and crucially, 6- NCs’ drug loading can be as high as 90%. This can be extremely useful in achieving therapeutic drug concentrations inside cells. Crucially, NCs can be administered via multiple administration routes, allowing a wide variety of therapeutic applications. In this project, you will modify the particle size and surface properties of drug NCs in order to obtain desirable characteristics for internalisation using our top-down methodology. The student will be in close contact with PhD students, Postdoctoral researchers, and members of staff that will support their research. Where possible, we will encourage the student to submit their work to scientific events and journals. Model fluorescent poorly soluble drugs will be used in this project. It will be milled using special vials equipped with jackets for water recirculation in order to control the temperature of the process. Multiple parameters will be adjusted to optimise the process, aiming to obtain NCs with mean particle sizes of ~100 nm. These variables include amount of milling beads, stirring speed, temperature, milling time, and drug loading. The surface of the NCs will be decorated using positively and negatively charges polymers as required.

Briefly describe the training that will be provided through the research project

Once NCs with desirable particle size and surface charges have been obtained, different characterisation techniques will be applied, including Fourier transformed infrared spectroscopy, X-ray diffraction, different microscopical analyses, and differential scanning calorimetry. Promising formulations will be tested in fibroblasts cell cultures where cell viability and internalisation will be assessed. Given the large number of techniques that will be used, the student is expected to enhance their technical skills as well to boost their soft skills by interacting with other members of our group.

Briefly outline the expected impact activities

We aim to address key knowledge gaps in the nanocrystals space, including new methods to produce finely-tuned nanocrystals and gain understanding on their interaction with biological surfaces. While doing that, the team will engage in dissemination and outreach activities to showcase project's updates.

Funding Notes

This project is not funded; applications are welcome from self-funding candidates.

References

Nanocrystals, nanomedicine, drug delivery, cell targeting