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“Squalenoylcurcumin” Nanoassemblies as Water‐Dispersible Drug Candidates with Antileishmanial Activity
Author(s) -
CheikhAli Zakaria,
Caron Joachim,
Cojean Sandrine,
Bories Christian,
Couvreur Patrick,
Loiseau Philippe M.,
Desmaële Didier,
Poupon Erwan,
Champy Pierre
Publication year - 2015
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201402449
Subject(s) - curcumin , miltefosine , chemistry , leishmania donovani , bioavailability , pharmacology , antiprotozoal , in vivo , leishmania , drug , leishmaniasis , visceral leishmaniasis , amastigote , in vitro , axenic , biochemistry , biology , immunology , microbiology and biotechnology , parasite hosting , genetics , world wide web , computer science , bacteria
Curcumin, a natural polyphenolic compound, showed antiparasitic potential, including trypanocidal and leishmanicidal activity, in several in vitro and in vivo models. The molecule is well tolerated in humans. However, it is insoluble in water and displays poor oral bioavailability as a result of low absorption. New derivatives of curcumin were prepared by esterification of one or two of its phenolic groups with 1,1′,2‐tris‐norsqualenic acid. These “squalenoylcurcumins” were formulated as water‐dispersible nanoassemblies of homogeneous size, and they proved to be stable. Squalenoylcurcumins were inactive against Trypanosoma brucei brucei trypomastigotes, even as nanoassemblies, in contrast with curcumin. However, against Leishmania donovani promastigotes, the activities of the squalenoylcurcumins and their nanoassemblies were enhanced relative to that of curcumin. In L. donovani axenic and intramacrophagic amastigotes, they showed activity in the range of miltefosine, with good selectivity indexes. In regard to their dispersibility in water and to the safety of curcumin, these nanoassemblies are promising candidates for preclinical study toward the treatment of visceral leishmaniasis.