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...
Saved in:
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2024-10-01
|
| Series: | Pharmaceutics |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1999-4923/16/11/1369 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1846152728838930432 |
|---|---|
| author | Tamara Ramos Maciel Ana Claudia Funguetto-Ribeiro Laura Ben Olivo Flávia Elizabete Guerra Teixeira Camila de Oliveira Pacheco Bibiana Verlindo de Araujo Sandra Elisa Haas |
| author_facet | Tamara Ramos Maciel Ana Claudia Funguetto-Ribeiro Laura Ben Olivo Flávia Elizabete Guerra Teixeira Camila de Oliveira Pacheco Bibiana Verlindo de Araujo Sandra Elisa Haas |
| author_sort | Tamara Ramos Maciel |
| collection | DOAJ |
| description | <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. |
| format | Article |
| id | doaj-art-9f8eb09493d145a2b3a73912f8ad4f0c |
| institution | Kabale University |
| issn | 1999-4923 |
| language | English |
| publishDate | 2024-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj-art-9f8eb09493d145a2b3a73912f8ad4f0c2024-11-26T18:17:43ZengMDPI AGPharmaceutics1999-49232024-10-011611136910.3390/pharmaceutics16111369Improved Malaria Therapy with Cationic Nanocapsules Demonstrated in <i>Plasmodium berghei</i>-Infected Rodents Using Whole Blood Surrogate Population PK/PD ModelingTamara Ramos Maciel0Ana Claudia Funguetto-Ribeiro1Laura Ben Olivo2Flávia Elizabete Guerra Teixeira3Camila de Oliveira Pacheco4Bibiana Verlindo de Araujo5Sandra Elisa Haas6Pharmacology and Pharmacometric Laboratory, LABFAR, Federal University of Pampa (UNIPAMPA), Uruguaiana 97501-970, RS, BrazilPharmacology and Pharmacometric Laboratory, LABFAR, Federal University of Pampa (UNIPAMPA), Uruguaiana 97501-970, RS, BrazilPharmaceutical Sciences Post Graduate Program, College of Pharmacy, Federal University of Rio Grande do Sul, Porto Alegre 91060-100, RS, BrazilPharmacology and Pharmacometric Laboratory, LABFAR, Federal University of Pampa (UNIPAMPA), Uruguaiana 97501-970, RS, BrazilPharmacology and Pharmacometric Laboratory, LABFAR, Federal University of Pampa (UNIPAMPA), Uruguaiana 97501-970, RS, BrazilPharmaceutical Sciences Post Graduate Program, College of Pharmacy, Federal University of Rio Grande do Sul, Porto Alegre 91060-100, RS, BrazilPharmacology and Pharmacometric Laboratory, LABFAR, Federal University of Pampa (UNIPAMPA), Uruguaiana 97501-970, RS, Brazil<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.https://www.mdpi.com/1999-4923/16/11/1369interspecies translationwhole bloodquininenanocapsulesmalariaPK/PD modeling |
| spellingShingle | Tamara Ramos Maciel Ana Claudia Funguetto-Ribeiro Laura Ben Olivo Flávia Elizabete Guerra Teixeira Camila de Oliveira Pacheco Bibiana Verlindo de Araujo Sandra Elisa Haas Improved Malaria Therapy with Cationic Nanocapsules Demonstrated in <i>Plasmodium berghei</i>-Infected Rodents Using Whole Blood Surrogate Population PK/PD Modeling Pharmaceutics interspecies translation whole blood quinine nanocapsules malaria PK/PD modeling |
| title | Improved Malaria Therapy with Cationic Nanocapsules Demonstrated in <i>Plasmodium berghei</i>-Infected Rodents Using Whole Blood Surrogate Population PK/PD Modeling |
| title_full | Improved Malaria Therapy with Cationic Nanocapsules Demonstrated in <i>Plasmodium berghei</i>-Infected Rodents Using Whole Blood Surrogate Population PK/PD Modeling |
| title_fullStr | Improved Malaria Therapy with Cationic Nanocapsules Demonstrated in <i>Plasmodium berghei</i>-Infected Rodents Using Whole Blood Surrogate Population PK/PD Modeling |
| title_full_unstemmed | Improved Malaria Therapy with Cationic Nanocapsules Demonstrated in <i>Plasmodium berghei</i>-Infected Rodents Using Whole Blood Surrogate Population PK/PD Modeling |
| title_short | Improved Malaria Therapy with Cationic Nanocapsules Demonstrated in <i>Plasmodium berghei</i>-Infected Rodents Using Whole Blood Surrogate Population PK/PD Modeling |
| title_sort | improved malaria therapy with cationic nanocapsules demonstrated in i plasmodium berghei i infected rodents using whole blood surrogate population pk pd modeling |
| topic | interspecies translation whole blood quinine nanocapsules malaria PK/PD modeling |
| url | https://www.mdpi.com/1999-4923/16/11/1369 |
| work_keys_str_mv | AT tamararamosmaciel improvedmalariatherapywithcationicnanocapsulesdemonstratediniplasmodiumbergheiiinfectedrodentsusingwholebloodsurrogatepopulationpkpdmodeling AT anaclaudiafunguettoribeiro improvedmalariatherapywithcationicnanocapsulesdemonstratediniplasmodiumbergheiiinfectedrodentsusingwholebloodsurrogatepopulationpkpdmodeling AT laurabenolivo improvedmalariatherapywithcationicnanocapsulesdemonstratediniplasmodiumbergheiiinfectedrodentsusingwholebloodsurrogatepopulationpkpdmodeling AT flaviaelizabeteguerrateixeira improvedmalariatherapywithcationicnanocapsulesdemonstratediniplasmodiumbergheiiinfectedrodentsusingwholebloodsurrogatepopulationpkpdmodeling AT camiladeoliveirapacheco improvedmalariatherapywithcationicnanocapsulesdemonstratediniplasmodiumbergheiiinfectedrodentsusingwholebloodsurrogatepopulationpkpdmodeling AT bibianaverlindodearaujo improvedmalariatherapywithcationicnanocapsulesdemonstratediniplasmodiumbergheiiinfectedrodentsusingwholebloodsurrogatepopulationpkpdmodeling AT sandraelisahaas improvedmalariatherapywithcationicnanocapsulesdemonstratediniplasmodiumbergheiiinfectedrodentsusingwholebloodsurrogatepopulationpkpdmodeling |