NDLI: N-(2-hydroxypropyl)methacrylamide–amphotericin B (HPMA–AmB) copolymer conjugates as antileishmanial agents

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N-(2-hydroxypropyl)methacrylamide–amphotericin B (HPMA–AmB) copolymer conjugates as antileishmanial agents

Content Provider	Semantic Scholar
Author	Nicoletti, Salvatore Seifert, Karin Gilbert, Ian H.
Copyright Year	2009
Abstract	Leishmaniasis is a major health problem in many parts of the world, caused by various species of Leishmania. Amastigotes are the clinically relevant form of the parasite in the human host and reside in the parasitophorous vacuole within macrophages. Polymer-drug conjugates have been used for lysosomotropic drug delivery and have already shown potential in anticancer and antileishmanial chemotherapy. We synthesised N-(2-hydroxypropyl)methacrylamide-amphotericin B (HPMA-AmB) copolymer conjugates in which the AmB was attached to the polymer through a degradable GlyPheLeuGly linker. Antileishmanial activity was assessed in vitro against intracellular amastigotes in host macrophages [murine peritoneal exudate macrophages (PEMs), murine bone marrow-derived macrophages (BMMs) and differentiated THP-1 cells]. The most potent copolymers had 50% effective concentration (EC(50)) values of 0.03 microg/mL AmB equivalent against Leishmania donovani amastigotes in PEMs and BMMs and an EC(50) of 0.57 microg/mL AmB equivalent against L. donovani in THP-1 cells. This activity was comparable with free AmB (EC(50)=0.03-0.07 microg/mL against L. donovani in PEMs and BMMs and 0.24-0.42 microg/mL against amastigotes in THP-1 cells) and Fungizone (EC(50)=0.04-0.07 microg/mL against amastigotes in PEMs). Conjugates also showed potent in vivo activity with ca. 50% inhibition of parasite burden at 1mg/kg body weight.
Starting Page	441
Ending Page	448
Page Count	8
File Format	PDF HTM / HTML
DOI	10.1016/j.ijantimicag.2008.10.013
PubMed reference number	19097763
Journal	Medline
Volume Number	33
Alternate Webpage(s)	http://researchonline.lshtm.ac.uk/5480/1/main.pdf
Alternate Webpage(s)	https://doi.org/10.1016/j.ijantimicag.2008.10.013
Journal	International journal of antimicrobial agents
Language	English
Access Restriction	Open
Content Type	Text
Resource Type	Article

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