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Synthesis and Characterization of a Biomimetic Formulation of Clofazimine Hydrochloride Microcrystals for Parenteral Administration
Clofazimine (CFZ) is a broad spectrum antimycobacterial agent recommended by the World Health Organization as a first line treatment for leprosy and second line treatment for multidrug resistant tuberculosis. Oral administration of CFZ leads to a red skin pigmentation side effect. Since CFZ is a wea...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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MDPI
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6321048/ https://www.ncbi.nlm.nih.gov/pubmed/30453628 http://dx.doi.org/10.3390/pharmaceutics10040238 |
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author | Murashov, Mikhail D. Diaz-Espinosa, Jennifer LaLone, Vernon Tan, Joel W. Y. Laza, Raluca Wang, Xueding Stringer, Kathleen A. Rosania, Gus R. |
author_facet | Murashov, Mikhail D. Diaz-Espinosa, Jennifer LaLone, Vernon Tan, Joel W. Y. Laza, Raluca Wang, Xueding Stringer, Kathleen A. Rosania, Gus R. |
author_sort | Murashov, Mikhail D. |
collection | PubMed |
description | Clofazimine (CFZ) is a broad spectrum antimycobacterial agent recommended by the World Health Organization as a first line treatment for leprosy and second line treatment for multidrug resistant tuberculosis. Oral administration of CFZ leads to a red skin pigmentation side effect. Since CFZ is a weakly basic, red phenazine dye, the skin pigmentation side effect results from lipophilic partitioning of the circulating, free base (neutral) form of CFZ into the skin. Here, we developed a stable and biocompatible formulation of CFZ-HCl microcrystals that mimics the predominant form of the drug that bioaccumulates in macrophages, following long term oral CFZ administration. In mice, intravenous injection of these biomimetic CFZ-HCl microcrystals led to visible drug accumulation in macrophages of the reticuloendothelial system with minimal skin accumulation or pigmentation. In fact, no skin pigmentation was observed when the total amount of CFZ-HCl administered was equivalent to the total oral dose leading to maximal skin pigmentation. Thus, parenteral (injected or inhaled) biomimetic formulations of CFZ-HCl could be instrumental to avoid the pigmentation side effect of oral CFZ therapy. |
format | Online Article Text |
id | pubmed-6321048 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-63210482019-01-11 Synthesis and Characterization of a Biomimetic Formulation of Clofazimine Hydrochloride Microcrystals for Parenteral Administration Murashov, Mikhail D. Diaz-Espinosa, Jennifer LaLone, Vernon Tan, Joel W. Y. Laza, Raluca Wang, Xueding Stringer, Kathleen A. Rosania, Gus R. Pharmaceutics Article Clofazimine (CFZ) is a broad spectrum antimycobacterial agent recommended by the World Health Organization as a first line treatment for leprosy and second line treatment for multidrug resistant tuberculosis. Oral administration of CFZ leads to a red skin pigmentation side effect. Since CFZ is a weakly basic, red phenazine dye, the skin pigmentation side effect results from lipophilic partitioning of the circulating, free base (neutral) form of CFZ into the skin. Here, we developed a stable and biocompatible formulation of CFZ-HCl microcrystals that mimics the predominant form of the drug that bioaccumulates in macrophages, following long term oral CFZ administration. In mice, intravenous injection of these biomimetic CFZ-HCl microcrystals led to visible drug accumulation in macrophages of the reticuloendothelial system with minimal skin accumulation or pigmentation. In fact, no skin pigmentation was observed when the total amount of CFZ-HCl administered was equivalent to the total oral dose leading to maximal skin pigmentation. Thus, parenteral (injected or inhaled) biomimetic formulations of CFZ-HCl could be instrumental to avoid the pigmentation side effect of oral CFZ therapy. MDPI 2018-11-17 /pmc/articles/PMC6321048/ /pubmed/30453628 http://dx.doi.org/10.3390/pharmaceutics10040238 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Murashov, Mikhail D. Diaz-Espinosa, Jennifer LaLone, Vernon Tan, Joel W. Y. Laza, Raluca Wang, Xueding Stringer, Kathleen A. Rosania, Gus R. Synthesis and Characterization of a Biomimetic Formulation of Clofazimine Hydrochloride Microcrystals for Parenteral Administration |
title | Synthesis and Characterization of a Biomimetic Formulation of Clofazimine Hydrochloride Microcrystals for Parenteral Administration |
title_full | Synthesis and Characterization of a Biomimetic Formulation of Clofazimine Hydrochloride Microcrystals for Parenteral Administration |
title_fullStr | Synthesis and Characterization of a Biomimetic Formulation of Clofazimine Hydrochloride Microcrystals for Parenteral Administration |
title_full_unstemmed | Synthesis and Characterization of a Biomimetic Formulation of Clofazimine Hydrochloride Microcrystals for Parenteral Administration |
title_short | Synthesis and Characterization of a Biomimetic Formulation of Clofazimine Hydrochloride Microcrystals for Parenteral Administration |
title_sort | synthesis and characterization of a biomimetic formulation of clofazimine hydrochloride microcrystals for parenteral administration |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6321048/ https://www.ncbi.nlm.nih.gov/pubmed/30453628 http://dx.doi.org/10.3390/pharmaceutics10040238 |
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