Periodic Reporting for period 1 - DeShield (Hide and Seek with Cancer Drugs)
Okres sprawozdawczy: 2017-06-01 do 2018-11-30
The DeShield project aimed at improving treatment options for neoplastic diseases by investigating a chemotherapeutic nanocarrier. This nanocarrier should accumulate at the site of disease due to a long circulation half-life conferred by a polymer shield. After accumulation, the shield should be removed by application of an external stimulus, thus improving the uptake of the drug by the diseased cells and improving therapeutic efficacy without escalating required doses.
This nanocarrier, previously developed and tested in vitro with promising results, was tested in initial in vivo experiments but failed to meet expectations of an increased plasma half life. Subsequently, no more in vivo experiments were performed for ethical reasons. Instead, a number of improvements to the system were designed and iteratively implemented and tested in further in vitro experiments.
First, the formulation of the nanocarrier proper was optimized in order to achieve an optimal balance between maximal inhibition of cellular interaction in the shielded state and maximal uptake of the nanocarrier by cells in the deshielded state.
Second, the interaction between the nanocarrier and the shielding polymer was further optimized to meet specifications in vivo. The cause for the reduction of interactions between the shielding layer and the nanocarrier was identified and addressed by a rationally designed approach. In addition, the valency of the interaction between both components was increased in order to provide more stable dynamic shielding in biological fluids, such as blood plasma.
With these improvements, we are now conducting further validation studies in vivo.
This nanocarrier, previously developed and tested in vitro with promising results, was tested in initial in vivo experiments but failed to meet expectations of an increased plasma half life. Subsequently, no more in vivo experiments were performed for ethical reasons. Instead, a number of improvements to the system were designed and iteratively implemented and tested in further in vitro experiments.
First, the formulation of the nanocarrier proper was optimized in order to achieve an optimal balance between maximal inhibition of cellular interaction in the shielded state and maximal uptake of the nanocarrier by cells in the deshielded state.
Second, the interaction between the nanocarrier and the shielding polymer was further optimized to meet specifications in vivo. The cause for the reduction of interactions between the shielding layer and the nanocarrier was identified and addressed by a rationally designed approach. In addition, the valency of the interaction between both components was increased in order to provide more stable dynamic shielding in biological fluids, such as blood plasma.
With these improvements, we are now conducting further validation studies in vivo.