Clozapine-loaded nanocapsules improve antipsychotic activity in rats: building a sequential PopPK/PD model to discriminate nanocarriers in the preformulation step

Funguetto-Ribeiro, Ana Cláudia; Maciel, Tamara Ramos; Lunardi, Annelize Gruppi; Gomes, Daniel Borges; Ibarra, Manuel; Haas, Sandra Elisa

doi:10.1007/s11095-023-03551-8

Pharm Res

2023

DOI: 10.1007/s11095-023-03551-8

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Clozapine-loaded nanocapsules improve antipsychotic activity in rats: building a sequential PopPK/PD model to discriminate nanocarriers in the preformulation step

Ana Cláudia Funguetto-Ribeiro,

Tamara Ramos Maciel,

Annelize Gruppi Lunardi

et al.

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2024

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Improved Malaria Therapy with Cationic Nanocapsules Demonstrated in Plasmodium berghei-Infected Rodents Using Whole Blood Surrogate Population PK/PD Modeling

Maciel,

Funguetto-Ribeiro,

Olivo

et al. 2024

Pharmaceutics

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Objectives: 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 Plasmodium berghei-infected mice, with a subsequent model comparison for nanocapsules coated with polysorbate (NCP80) or prepared with Eudragit® 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. Results: 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. Conclusions: 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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Improved Malaria Therapy with Cationic Nanocapsules Demonstrated in Plasmodium berghei-Infected Rodents Using Whole Blood Surrogate Population PK/PD Modeling

Maciel,

Funguetto-Ribeiro,

Olivo

et al. 2024

Pharmaceutics

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Clozapine-loaded nanocapsules improve antipsychotic activity in rats: building a sequential PopPK/PD model to discriminate nanocarriers in the preformulation step

Cited by 1 publication

References 53 publications

Improved Malaria Therapy with Cationic Nanocapsules Demonstrated in Plasmodium berghei-Infected Rodents Using Whole Blood Surrogate Population PK/PD Modeling

Improved Malaria Therapy with Cationic Nanocapsules Demonstrated in Plasmodium berghei-Infected Rodents Using Whole Blood Surrogate Population PK/PD Modeling

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