Per Hansson
Uppsala University, Sweden
Biography
Prof. Per Hansson has his expertise in colloidal systems of relevance for developing drug delivery systems. Most of his studies have dealt with polyelectrolytes and their interaction with colloids of opposite charge, in particularly phase transitions and phase separation in polyelectrolyte hydrogels in relation to the loading and release of amphiphilic drugs, proteins and peptides. He is currently investigating the self-assembling properties of amphiphilic drugs, and the fate of biomacromolecular drug formulations after injection into the subcutaneous tissue. This involves the development of in vitro methods to study the release from formulations and transport through the extracellular matrix. Hansson is leading the Pharmaceutical Physical Chemistry group at the Department of Pharmacy, Uppsala University, and the Parenteral Drug Delivery Platform of the Swedish Drug Delivery Forum
Abstract
Statement of the Problem: Microgels have the capacity to store large amounts of amphiphilic, peptide and protein drugs. This makes them interesting as delivery systems for drugs needing protection against degradation, and as components of slow-release and depot formulations for parenteral administration. Despite the fact that microgels are used clinically, e.g., to deliver doxorubicin in the treatment of liver cancer [1], little attention has been given to how the drug self-assembly inside microgels affects the release properties. The purpose of this study is to show that that the release of amphiphilic drugs is strongly influenced by self-assembly [2] and its effect on the swelling of the microgel network. Methodology & Theory: Loading and release of cationic amphiphilic drugs are investigate by means of micropipette-assisted microscopy of single microgels [2, 3] (Fig. 1) and μDiss apparatus studies. We have developed and evaluated two new models combining transport dynamics and thermodynamics of drug self-assembly, one for non- swelling responsive microgels based on the Nernst-Planck equation [2], and one for responsive networks handling coexisting phases with different degrees of network swelling. Findings: For two polyelectrolyte microgel systems, DC bead® used clinically, and polyacrylate microspheres (diameter: ~100 μm), the drug self-assembly has a profound effect on the loading and release kinetics as well as on the distribution of the drug inside the beads and the distribution between different beads in a suspension. The roles played by salt in the release medium and the responsiveness of the polymer network are highlighted. The micropipette technique is found to be a powerful in vitro method. Conclusions & Significance: The results highlight the importance of the electric coupling of diffusive fluxes, the amphiphilic self-assembly and the responsiveness of the microgel. The results are important for the development of microgel drug delivery systems with improved release kinetics