WP 3: Drug release kinetics study

LEADER: IPF (prof. A. Lederer)

PARTNERS: IPF & StU

OBJECTIVES:

• Determination of stability, degradation and drug release kinetics.

• Mathematical modelling of response to treatments of infectious diseases.

DELIVERABLES

10.2022 M 3.1

Robust analytical approach for particle size and conformation and degradation profile established.

01.2023 D 3.1

Established correlation between; (i) macromolecular structure/composition and particles size, conformation, degradation, loading capacity and drug release and (ii) lipid nanoparticle size, degradation, loading capacity and drug release. (IPF)

04.2023 D 3.2

Quantification of drug effects on glycolytic flux and specific growth rate in vitro. Determination of mode of action and including drug in existing detailed mathematical model for glycolysis (direct effect on glycolysis). Determination of the drug effect on growth rate in core model for growth of asexual stages (no effect on glycolysis). Construction of a core model for growth of sexual stages in vitro with drug effect. (StU)

10.2023 D 3.3

Calibration of the in vitro models for growth to in vivo situation, analysis of drug release dynamic data from WP 4 and WP5 and development of PK/PD models. (StU)

01.2024 D 3.5

Interplay between hydrogel-matrix swelling and degradation and hydrophobic / amphiphilic nanoparticle release is clarified. One multicomponent matrix with characterized release profiles for in vitro and in vivo evaluation established. (IPF)

04.2024 M 3.2

Multistep-release profiles from one multicomponent matrix of one anti-malaria and one anti-transmission drug have been determined

01.2024 D 3.4

Calculation of optimal drug release dynamics in the PK/PD model that includes growth models, drug release and drug clearance rates specifically for the different parasite stages. (i.e. shorter for the asexual stages, longer for the sexual stages). (StU)