Formulation of Amphotericin B in PEGylated Liposomes for Improved Treatment of Cutaneous Leishmaniasis by Parenteral and Oral Routes
Liposomal amphotericin B (AmB) or AmBisome<sup>®</sup> is the most effective and safe therapeutic agent for visceral leishmaniasis (VL), but its clinical efficacy is limited in cutaneous leishmaniasis (CL) and HIV/VL co-infection. The aim of this work was to develop a formulation of AmB...
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MDPI AG
2022-05-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/14/5/989 |
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| author | Guilherme S. Ramos Virgínia M. R. Vallejos Gabriel S. M. Borges Raquel M. Almeida Izabela M. Alves Marta M. G. Aguiar Christian Fernandes Pedro P. G. Guimarães Ricardo T. Fujiwara Philippe M. Loiseau Lucas A. M. Ferreira Frédéric Frézard |
| author_facet | Guilherme S. Ramos Virgínia M. R. Vallejos Gabriel S. M. Borges Raquel M. Almeida Izabela M. Alves Marta M. G. Aguiar Christian Fernandes Pedro P. G. Guimarães Ricardo T. Fujiwara Philippe M. Loiseau Lucas A. M. Ferreira Frédéric Frézard |
| author_sort | Guilherme S. Ramos |
| collection | DOAJ |
| description | Liposomal amphotericin B (AmB) or AmBisome<sup>®</sup> is the most effective and safe therapeutic agent for visceral leishmaniasis (VL), but its clinical efficacy is limited in cutaneous leishmaniasis (CL) and HIV/VL co-infection. The aim of this work was to develop a formulation of AmB in PEGylated liposomes and compare its efficacy to AmBisome<sup>®</sup> in a murine model of CL. Formulations of AmB in conventional and PEGylated liposomes were characterized for particle size and morphology, drug encapsulation efficiency and aggregation state. Those were compared to AmBisome<sup>®</sup> in <i>Leishmania amazonensis</i>-infected BALB/c mice for their effects on the lesion size growth and parasite load. The conventional and PEGylated formulations showed vesicles with 100–130 nm diameter and low polydispersity, incorporating more than 95% of AmB under the non-aggregated form. Following parenteral administration in the murine model of CL, the PEGylated formulation of AmB significantly reduced the lesion size growth and parasite load, in comparison to control groups, in contrast to conventional liposomal AmB. The PEGylated formulation of AmB was also effective when given by oral route on a 2-day regimen. This work reports for the first time that PEGylated liposomal AmB can improve the treatment of experimental cutaneous leishmaniasis by both parenteral and oral routes. |
| first_indexed | 2024-03-10T03:07:17Z |
| format | Article |
| id | doaj.art-21924717897c46609603ca3cfbced1c3 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-10T03:07:17Z |
| publishDate | 2022-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-21924717897c46609603ca3cfbced1c32023-11-23T12:37:43ZengMDPI AGPharmaceutics1999-49232022-05-0114598910.3390/pharmaceutics14050989Formulation of Amphotericin B in PEGylated Liposomes for Improved Treatment of Cutaneous Leishmaniasis by Parenteral and Oral RoutesGuilherme S. Ramos0Virgínia M. R. Vallejos1Gabriel S. M. Borges2Raquel M. Almeida3Izabela M. Alves4Marta M. G. Aguiar5Christian Fernandes6Pedro P. G. Guimarães7Ricardo T. Fujiwara8Philippe M. Loiseau9Lucas A. M. Ferreira10Frédéric Frézard11Department of Physiology and Biophysics, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, MG, BrazilDepartment of Physiology and Biophysics, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, MG, BrazilFaculty of Pharmacy, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, MG, BrazilDepartment of Parasitology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, MG, BrazilFaculty of Pharmacy, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, MG, BrazilFaculty of Pharmacy, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, MG, BrazilFaculty of Pharmacy, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, MG, BrazilDepartment of Physiology and Biophysics, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, MG, BrazilDepartment of Parasitology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, MG, BrazilFaculty of Pharmacy, Antiparasite Chemotherapy, UMR 8076 CNRS BioCIS, University Paris-Saclay, F-92296 Chatenay-Malabry, FranceFaculty of Pharmacy, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, MG, BrazilDepartment of Physiology and Biophysics, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, MG, BrazilLiposomal amphotericin B (AmB) or AmBisome<sup>®</sup> is the most effective and safe therapeutic agent for visceral leishmaniasis (VL), but its clinical efficacy is limited in cutaneous leishmaniasis (CL) and HIV/VL co-infection. The aim of this work was to develop a formulation of AmB in PEGylated liposomes and compare its efficacy to AmBisome<sup>®</sup> in a murine model of CL. Formulations of AmB in conventional and PEGylated liposomes were characterized for particle size and morphology, drug encapsulation efficiency and aggregation state. Those were compared to AmBisome<sup>®</sup> in <i>Leishmania amazonensis</i>-infected BALB/c mice for their effects on the lesion size growth and parasite load. The conventional and PEGylated formulations showed vesicles with 100–130 nm diameter and low polydispersity, incorporating more than 95% of AmB under the non-aggregated form. Following parenteral administration in the murine model of CL, the PEGylated formulation of AmB significantly reduced the lesion size growth and parasite load, in comparison to control groups, in contrast to conventional liposomal AmB. The PEGylated formulation of AmB was also effective when given by oral route on a 2-day regimen. This work reports for the first time that PEGylated liposomal AmB can improve the treatment of experimental cutaneous leishmaniasis by both parenteral and oral routes.https://www.mdpi.com/1999-4923/14/5/989liposomesamphotericin Bleishmaniasisoral routePEGylationcutaneous leishmaniasis |
| spellingShingle | Guilherme S. Ramos Virgínia M. R. Vallejos Gabriel S. M. Borges Raquel M. Almeida Izabela M. Alves Marta M. G. Aguiar Christian Fernandes Pedro P. G. Guimarães Ricardo T. Fujiwara Philippe M. Loiseau Lucas A. M. Ferreira Frédéric Frézard Formulation of Amphotericin B in PEGylated Liposomes for Improved Treatment of Cutaneous Leishmaniasis by Parenteral and Oral Routes Pharmaceutics liposomes amphotericin B leishmaniasis oral route PEGylation cutaneous leishmaniasis |
| title | Formulation of Amphotericin B in PEGylated Liposomes for Improved Treatment of Cutaneous Leishmaniasis by Parenteral and Oral Routes |
| title_full | Formulation of Amphotericin B in PEGylated Liposomes for Improved Treatment of Cutaneous Leishmaniasis by Parenteral and Oral Routes |
| title_fullStr | Formulation of Amphotericin B in PEGylated Liposomes for Improved Treatment of Cutaneous Leishmaniasis by Parenteral and Oral Routes |
| title_full_unstemmed | Formulation of Amphotericin B in PEGylated Liposomes for Improved Treatment of Cutaneous Leishmaniasis by Parenteral and Oral Routes |
| title_short | Formulation of Amphotericin B in PEGylated Liposomes for Improved Treatment of Cutaneous Leishmaniasis by Parenteral and Oral Routes |
| title_sort | formulation of amphotericin b in pegylated liposomes for improved treatment of cutaneous leishmaniasis by parenteral and oral routes |
| topic | liposomes amphotericin B leishmaniasis oral route PEGylation cutaneous leishmaniasis |
| url | https://www.mdpi.com/1999-4923/14/5/989 |
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