Nano-vehicles for Drug-delivery

Nano-vehicles for Delivery of Therapeutic Drugs and Antibiotics

When Paul Ehrlich first introduced the concept of selective drug delivery in the early 19th century [1]; he described “a magic bullet” – a specific carrier to bring the active pharmaceutical ingredient (API) to the desired location of action. In this way, side effects, which sometimes can provoke severe complication or even inhibit treatment, are minimized since the free drug will not be present in the bloodstream.  While a “magic bullet” is not likely to exist, block copolymers or peptides that self-assemble into well-defined nanostructures might be promising substitutes as nano-carrier to bring drugs to a predefined location in the organ, tissue or cell.

Solubilisation of hydrophobic drugs in nanocarriers has a significant potential as about 50% of the new drug formulations coming to the market need a carrier to be distributed in the body due to their low solubility in biological fluids. While some examples of drugs carried in polymeric micelles in fact are under clinical testing, there are many challenges and problems to overcome before it can be a significant success. Frequent problems include, low encapsulation efficiency, rapid leaking, change and even dissolution of the micellar aggregates. In addition, there is the problem of specificity, each drug is different and a design of a carrier that effectively takes up that particular drug needs to be found. Also, very crucially, the carrier itself must be biocompatible and not contain or degrade into cytotoxic products.  Finally, the kinetics of release of the drug at the desired location must take place at a desired time scale. Ideally one would prefer a “burst release” of the drug in the region of interest.  This would require some sort of trigger or stimuli. In the first approximation and in fact the primary objective of such delivery systems is protection of the drug and slow release into the body.

Figure: Illustration of the block copolymer/peptide self-assembly into micelles and solubilisation of drug molecules. In this way both hydrophobic and hydrophilic drugs can be encapsulated and protected.

Our projects
  • Role of crystallinity on the solubilization of therapeutics in micellar cores
  • Transport through vesicular polymeric nanostructures
Active group members
  • Post Doc Matthias Amann
  • MSc. student Mikkel Killingmoe Christensen
Publications
  • Xu, D. et al. Designed supramolecular filamentous peptides: balance of nanostructure, cytotoxicity and antimicrobial activity. Commun. 51, 1289–1292 (2014).
  • Yang, M. et al. Filamentous supramolecular peptide–drug conjugates as highly efficient drug delivery vehicles. Commun. 50, 4827–4830 (2014).
  • Trousil, J. et al. System with embedded drug release and nanoparticle degradation sensor showing efficient rifampicin delivery into macrophages. Nanomedicine: Nanotechnology, Biology, and Medicine 13, 307–315 (2017).
  • Medel, S. et al. Curcumin-bortezomib loaded polymeric nanoparticles for synergistic cancer therapy. European Polymer Journal 93, 116–131 (2017).