Improved Malaria Therapy with Cationic Nanocapsules Demonstrated in <i>Plasmodium berghei</i>-Infected Rodents Using Whole Blood Surrogate Population PK/PD Modeling
<b>Objectives</b>: Investigating how nanoparticle systems interact in whole blood (WB) is critical to evaluating the effectiveness of malaria therapy. Methods: We decided to establish a pharmacokinetic/pharmacodynamic (PK/PD) model of the quinine population in WB using <i>Plasmodiu...
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| Main Authors: | , , , , , , |
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| Format: | Book |
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MDPI AG,
2024-10-01T00:00:00Z.
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| Summary: | <b>Objectives</b>: Investigating how nanoparticle systems interact in whole blood (WB) is critical to evaluating the effectiveness of malaria therapy. Methods: We decided to establish a pharmacokinetic/pharmacodynamic (PK/PD) model of the quinine population in WB using <i>Plasmodium berghei</i>-infected mice, with a subsequent model comparison for nanocapsules coated with polysorbate (NCP80) or prepared with Eudragit<sup>®</sup> RS (NCEUD). The WB quinine population pharmacokinetic model in rats was developed using plasma and partition coefficients for rat erythrocytes. Mouse WB quinine population PK/PD modeling was developed using allometrically scaled literature-free mouse quinine pharmacokinetic data and covariate values to obtain a WB population pharmacokinetic model for quinine and nanocapsules in mice. This allowed for PK/PD modeling of the quinine population with the WB concentration and parasitemia data in mice. All models were built in NONMEN. <b>Results</b>: The WB quinine concentration profiles in rats were characterized using a two-compartment model. Nanoencapsulation reduced clearance and central compartment volume and increased peripherical compartimental volume. A maximum effect model described the PK/PD of the quinine WB population in mice, demonstrating that NCEUD enhances the antimalarial effect. <b>Conclusions</b>: Quinine WB is a good surrogate for describing the response to exposure in malaria. NCEUD outperformed NCP80 and free quinine, suggesting that cationic surfaces improve the potential for treating malaria. |
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| Item Description: | 10.3390/pharmaceutics16111369 1999-4923 |