Decoquinate liposomes: highly effective clearance of Plasmodium parasites causing severe malaria
Abstract Background Severe malaria caused by Plasmodium falciparum leads to most malaria-related deaths globally. Decoquinate (DQ) displays strong activity against multistage infection by Plasmodium parasites. However, the development of DQ as an oral dosage form for the treatment of malaria at the...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-01-01
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| Series: | Malaria Journal |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12936-022-04042-8 |
| _version_ | 1818306169193627648 |
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| author | Sumei Zeng Hongxing Wang Long Tao Xiaohui Ning Yinzhou Fan Siting Zhao Li Qin Xiaoping Chen |
| author_facet | Sumei Zeng Hongxing Wang Long Tao Xiaohui Ning Yinzhou Fan Siting Zhao Li Qin Xiaoping Chen |
| author_sort | Sumei Zeng |
| collection | DOAJ |
| description | Abstract Background Severe malaria caused by Plasmodium falciparum leads to most malaria-related deaths globally. Decoquinate (DQ) displays strong activity against multistage infection by Plasmodium parasites. However, the development of DQ as an oral dosage form for the treatment of malaria at the blood stage has not been successful. In this study, liposome formulations of DQ were created for intravenous (IV) injection to suppress Plasmodium berghei, a parasite that causes severe malaria in mice. Methods DQ liposomes were prepared by conventional ethanol injection method with slight modifications and encapsulation efficiency evaluated by the well-established centrifugation method. Potency of the DQ liposomes against P. falciparum was assessed in vitro using freshly isolated human red blood cells. The efficacy of the DQ liposomes was examined in the mouse model of severe malaria. Results The DQ liposomes were around 150 nm in size and had the encapsulation efficiency rates > 95%. The freshly prepared and lyophilized liposomes were stable after storage at − 20 °C for 6 months. The liposomes were shown to have excellent activity against P. falciparum in vitro with DQ IC50 0.91 ± 0.05 nM for 3D7 (chloroquine sensitive strain) and DQ IC50 1.33 ± 0.14 nM for Dd2 (multidrug resistant strain), which were 18- and 14-fold more potent than artemisinin, respectively. Mice did not have any signs of toxicity after receiving high dose of the liposomes (DQ 500 mg/kg per mouse) by IV injection. In the mouse model of severe malaria, the liposomes had impressive efficacy against P. berghei with DQ ED50 of 0.720 mg/kg. Conclusion The DQ liposomes prepared in this study were stable for long term storage and safe for IV injection in mammalian animals. The newly created liposome formulations had excellent activity against Plasmodium infection at the blood-stage, which encourages their application in the treatment of severe malaria. |
| first_indexed | 2024-12-13T06:38:12Z |
| format | Article |
| id | doaj.art-3674b782866c4cedbd7cf43492138a3b |
| institution | Directory Open Access Journal |
| issn | 1475-2875 |
| language | English |
| last_indexed | 2024-12-13T06:38:12Z |
| publishDate | 2022-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Malaria Journal |
| spelling | doaj.art-3674b782866c4cedbd7cf43492138a3b2022-12-21T23:56:29ZengBMCMalaria Journal1475-28752022-01-0121111410.1186/s12936-022-04042-8Decoquinate liposomes: highly effective clearance of Plasmodium parasites causing severe malariaSumei Zeng0Hongxing Wang1Long Tao2Xiaohui Ning3Yinzhou Fan4Siting Zhao5Li Qin6Xiaoping Chen7Guangzhou Bluelight Pharmaceutical Technology Co., Ltd, International Business IncubatorGuangzhou Bluelight Pharmaceutical Technology Co., Ltd, International Business IncubatorGuangzhou Bluelight Pharmaceutical Technology Co., Ltd, International Business IncubatorGuangzhou Bluelight Pharmaceutical Technology Co., Ltd, International Business IncubatorGuangzhou Bluelight Pharmaceutical Technology Co., Ltd, International Business IncubatorCAS Lamvac Biotech Co. Ltd, International Business IncubatorCAS Lamvac Biotech Co. Ltd, International Business IncubatorCAS Lamvac Biotech Co. Ltd, International Business IncubatorAbstract Background Severe malaria caused by Plasmodium falciparum leads to most malaria-related deaths globally. Decoquinate (DQ) displays strong activity against multistage infection by Plasmodium parasites. However, the development of DQ as an oral dosage form for the treatment of malaria at the blood stage has not been successful. In this study, liposome formulations of DQ were created for intravenous (IV) injection to suppress Plasmodium berghei, a parasite that causes severe malaria in mice. Methods DQ liposomes were prepared by conventional ethanol injection method with slight modifications and encapsulation efficiency evaluated by the well-established centrifugation method. Potency of the DQ liposomes against P. falciparum was assessed in vitro using freshly isolated human red blood cells. The efficacy of the DQ liposomes was examined in the mouse model of severe malaria. Results The DQ liposomes were around 150 nm in size and had the encapsulation efficiency rates > 95%. The freshly prepared and lyophilized liposomes were stable after storage at − 20 °C for 6 months. The liposomes were shown to have excellent activity against P. falciparum in vitro with DQ IC50 0.91 ± 0.05 nM for 3D7 (chloroquine sensitive strain) and DQ IC50 1.33 ± 0.14 nM for Dd2 (multidrug resistant strain), which were 18- and 14-fold more potent than artemisinin, respectively. Mice did not have any signs of toxicity after receiving high dose of the liposomes (DQ 500 mg/kg per mouse) by IV injection. In the mouse model of severe malaria, the liposomes had impressive efficacy against P. berghei with DQ ED50 of 0.720 mg/kg. Conclusion The DQ liposomes prepared in this study were stable for long term storage and safe for IV injection in mammalian animals. The newly created liposome formulations had excellent activity against Plasmodium infection at the blood-stage, which encourages their application in the treatment of severe malaria.https://doi.org/10.1186/s12936-022-04042-8DecoquinateLiposomesSevere malariaPlasmodium |
| spellingShingle | Sumei Zeng Hongxing Wang Long Tao Xiaohui Ning Yinzhou Fan Siting Zhao Li Qin Xiaoping Chen Decoquinate liposomes: highly effective clearance of Plasmodium parasites causing severe malaria Malaria Journal Decoquinate Liposomes Severe malaria Plasmodium |
| title | Decoquinate liposomes: highly effective clearance of Plasmodium parasites causing severe malaria |
| title_full | Decoquinate liposomes: highly effective clearance of Plasmodium parasites causing severe malaria |
| title_fullStr | Decoquinate liposomes: highly effective clearance of Plasmodium parasites causing severe malaria |
| title_full_unstemmed | Decoquinate liposomes: highly effective clearance of Plasmodium parasites causing severe malaria |
| title_short | Decoquinate liposomes: highly effective clearance of Plasmodium parasites causing severe malaria |
| title_sort | decoquinate liposomes highly effective clearance of plasmodium parasites causing severe malaria |
| topic | Decoquinate Liposomes Severe malaria Plasmodium |
| url | https://doi.org/10.1186/s12936-022-04042-8 |
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