Toxicology and drug delivery by cucurbit[n]uril type molecular containers.

<h4>Background</h4>Many drug delivery systems are based on the ability of certain macrocyclic compounds - such as cyclodextrins (CDs) - to act as molecular containers for pharmaceutical agents in water. Indeed beta-CD and its derivatives have been widely used in the formulation of hydrop...

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Autores principales:	Gaya Hettiarachchi, Duc Nguyen, Jing Wu, Derick Lucas, Da Ma, Lyle Isaacs, Volker Briken
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2010
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/cfe60645f0a54720809dfea2241a8141
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spelling	oai:doaj.org-article:cfe60645f0a54720809dfea2241a81412021-12-02T20:21:51ZToxicology and drug delivery by cucurbit[n]uril type molecular containers.1932-620310.1371/journal.pone.0010514https://doaj.org/article/cfe60645f0a54720809dfea2241a81412010-05-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20463906/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Many drug delivery systems are based on the ability of certain macrocyclic compounds - such as cyclodextrins (CDs) - to act as molecular containers for pharmaceutical agents in water. Indeed beta-CD and its derivatives have been widely used in the formulation of hydrophobic pharmaceuticals despite their poor abilities to act as a molecular container (e.g., weak binding (K(a)<10(4) M(-1)) and their challenges toward chemical functionalization. Cucurbit[n]urils (CB[n]) are a class of molecular containers that bind to a variety of cationic and neutral species with high affinity (K(a)>10(4) M(-1)) and therefore show great promise as a drug delivery system.<h4>Methodology</h4>In this study we investigated the toxicology, uptake, and bioactivity of two cucurbit[n]urils (CB[5] and CB[7]) and three CB[n]-type containers (Pentamer 1, methyl hexamer 2, and phenyl hexamer 3). All five containers demonstrated high cell tolerance at concentrations of up to 1 mM in cell lines originating from kidney, liver or blood tissue using assays for metabolic activity and cytotoxicity. Furthermore, the CB[7] molecular container was efficiently internalized by macrophages indicating their potential for the intracellular delivery of drugs. Bioactivity assays showed that the first-line tuberculosis drug, ethambutol, was as efficient in treating mycobacteria infected macrophages when loaded into CB[7] as when given in the unbound form. This result suggests that CB[7]-bound drug molecules can be released from the container to find their intracellular target.<h4>Conclusion</h4>Our study reveals very low toxicity of five members of the cucurbit[n]uril family of nanocontainers. It demonstrates the uptake of containers by cells and intracellular release of container-loaded drugs. These results provide initial proof-of-concept towards the use of CB[n] molecular containers as an advanced drug delivery system.Gaya HettiarachchiDuc NguyenJing WuDerick LucasDa MaLyle IsaacsVolker BrikenPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 5, Iss 5, p e10514 (2010)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Gaya Hettiarachchi Duc Nguyen Jing Wu Derick Lucas Da Ma Lyle Isaacs Volker Briken Toxicology and drug delivery by cucurbit[n]uril type molecular containers.
description	<h4>Background</h4>Many drug delivery systems are based on the ability of certain macrocyclic compounds - such as cyclodextrins (CDs) - to act as molecular containers for pharmaceutical agents in water. Indeed beta-CD and its derivatives have been widely used in the formulation of hydrophobic pharmaceuticals despite their poor abilities to act as a molecular container (e.g., weak binding (K(a)<10(4) M(-1)) and their challenges toward chemical functionalization. Cucurbit[n]urils (CB[n]) are a class of molecular containers that bind to a variety of cationic and neutral species with high affinity (K(a)>10(4) M(-1)) and therefore show great promise as a drug delivery system.<h4>Methodology</h4>In this study we investigated the toxicology, uptake, and bioactivity of two cucurbit[n]urils (CB[5] and CB[7]) and three CB[n]-type containers (Pentamer 1, methyl hexamer 2, and phenyl hexamer 3). All five containers demonstrated high cell tolerance at concentrations of up to 1 mM in cell lines originating from kidney, liver or blood tissue using assays for metabolic activity and cytotoxicity. Furthermore, the CB[7] molecular container was efficiently internalized by macrophages indicating their potential for the intracellular delivery of drugs. Bioactivity assays showed that the first-line tuberculosis drug, ethambutol, was as efficient in treating mycobacteria infected macrophages when loaded into CB[7] as when given in the unbound form. This result suggests that CB[7]-bound drug molecules can be released from the container to find their intracellular target.<h4>Conclusion</h4>Our study reveals very low toxicity of five members of the cucurbit[n]uril family of nanocontainers. It demonstrates the uptake of containers by cells and intracellular release of container-loaded drugs. These results provide initial proof-of-concept towards the use of CB[n] molecular containers as an advanced drug delivery system.
format	article
author	Gaya Hettiarachchi Duc Nguyen Jing Wu Derick Lucas Da Ma Lyle Isaacs Volker Briken
author_facet	Gaya Hettiarachchi Duc Nguyen Jing Wu Derick Lucas Da Ma Lyle Isaacs Volker Briken
author_sort	Gaya Hettiarachchi
title	Toxicology and drug delivery by cucurbit[n]uril type molecular containers.
title_short	Toxicology and drug delivery by cucurbit[n]uril type molecular containers.
title_full	Toxicology and drug delivery by cucurbit[n]uril type molecular containers.
title_fullStr	Toxicology and drug delivery by cucurbit[n]uril type molecular containers.
title_full_unstemmed	Toxicology and drug delivery by cucurbit[n]uril type molecular containers.
title_sort	toxicology and drug delivery by cucurbit[n]uril type molecular containers.
publisher	Public Library of Science (PLoS)
publishDate	2010
url	https://doaj.org/article/cfe60645f0a54720809dfea2241a8141
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Toxicology and drug delivery by cucurbit[n]uril type molecular containers.

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