Dual Nanoparticle-Driven Therapeutics for Leishmaniasis: A Mathematical Model of Targeted Macrophage and Parasite Elimination
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Background
To control leishmaniasis, chemotherapy drugs are currently under development. However, these drugs often exhibit poor efficacy and are associated with toxicity, adverse effects, and drug resistance. At present, no specific drug is available for the treatment of leishmaniasis. Meanwhile, vaccine research is ongoing. Recent studies have analysed some experimental vaccines using mathematical models.
Aim
In previous work, drug targeting was focused on the entire human body rather than specifically addressing infected macrophages and parasites. In our current approach, we aim to eliminate infected macrophages and parasites through nano-drug design. Specifically, we utilise two types of nanoparticles: iron oxide and citric acid–coated iron oxide. Moving forward, we plan to advance this strategy using mathematical modelling of macrophage–parasite interactions.
Methods
We design PDE-based models of macrophages and parasites, incorporating cytokine dynamics, to support nano-drug development. Drug efficacy is estimated using posterior distributions to analyse phenotypic fluctuations of macrophages and parasites during the design phase. We investigate implicit and semi-implicit treatment schemes, focusing on energy decay properties. To model drug flow during treatment, we introduce a three-phase moving boundary problem. Comparative analyses are conducted to evaluate macrophage and parasite behaviour with and without treatment. Finally, the entire framework is implemented within a virtual lab environment.
Results
The results show that the nano-drug exhibits better efficacy compared to combined drug doses. We analysed and compared two types of nano-drug particles: iron oxide and citric acid–coated iron oxide. We discuss how the drug effectively targets and eliminates infected macrophages and parasites.
Conclusion
Our model’s results and simulations will support researchers conducting further studies in nano-drug design for leishmaniasis. These simulations are performed within a virtual lab environment.
