Cytostatic effect of xanthone-loaded mPEG-b-p(HPMAm-Lac 2) micelles towards doxorubicin sensitive and resistant cancer cells

Xanthone exhibits several medicinal activities and especially it inhibits the growth of cancer cells. However, the use of xanthone is limited because of its low aqueous solubility and systemic toxicity. In the present study xanthone was loaded into poly(ethylene glycol)-b-poly[N-(2-hydroxypropyl) me...

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Main Authors: Khonkarn R., Mankhetkorn S., Talelli M., Hennink W.E., Okonogi S.
Format: Article
Language:English
Published: 2014
Online Access:http://www.scopus.com/inward/record.url?eid=2-s2.0-84859157763&partnerID=40&md5=ada4a27f53c7906ba838c31e20d957c8
http://cmuir.cmu.ac.th/handle/6653943832/4669
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spelling th-cmuir.6653943832-46692014-08-30T02:42:43Z Cytostatic effect of xanthone-loaded mPEG-b-p(HPMAm-Lac 2) micelles towards doxorubicin sensitive and resistant cancer cells Khonkarn R. Mankhetkorn S. Talelli M. Hennink W.E. Okonogi S. Xanthone exhibits several medicinal activities and especially it inhibits the growth of cancer cells. However, the use of xanthone is limited because of its low aqueous solubility and systemic toxicity. In the present study xanthone was loaded into poly(ethylene glycol)-b-poly[N-(2-hydroxypropyl) methacrylamide-dilactate] mPEG-b-p(HPMAm-Lac 2) micelles in order to overcome these drawbacks. It was shown that xanthone could be loaded in these micelles up to 2mg/mL with ∼100% entrapment efficiency and ∼20% loading capacity. The average particle diameter of the xanthone loaded mPEG-b-p(HPMAm-Lac 2) micelles as determined by dynamic light scattering ranged from 84 to 112nm. In vitro assays showed that xanthone in its free form as well as loaded in polymeric micelles had a high cytotoxicity towards both doxorubicin sensitive and, importantly, resistant cancer cells. On the other hand empty mPEG-b-p(HPMAm-Lac 2) micelles did not show any cytotoxicity towards normal cells (PBMCs). Interestingly, the cytostatic effect of xanthone towards normal cells was masked when loaded in the micelles. The mechanism of cell growth inhibition by xanthone-loaded polymeric micelles was mediated through induction of apoptosis, as evidenced from a subdiploid peak of propidium iodide stained cells using flow cytometric analysis. From the results of this study it can be concluded that xanthone has potent anticancer activity not only on sensitive but also on doxorubicin resistant cancer cell lines. mPEG-b-p(HPMAm-Lac 2) micelles are therefore attractive delivery systems of xanthone for the treatment of cancer. © 2012 Elsevier B.V. 2014-08-30T02:42:43Z 2014-08-30T02:42:43Z 2012 Article 9277765 10.1016/j.colsurfb.2012.02.002 22377215 CSBBE http://www.scopus.com/inward/record.url?eid=2-s2.0-84859157763&partnerID=40&md5=ada4a27f53c7906ba838c31e20d957c8 http://cmuir.cmu.ac.th/handle/6653943832/4669 English
institution Chiang Mai University
building Chiang Mai University Library
country Thailand
collection CMU Intellectual Repository
language English
description Xanthone exhibits several medicinal activities and especially it inhibits the growth of cancer cells. However, the use of xanthone is limited because of its low aqueous solubility and systemic toxicity. In the present study xanthone was loaded into poly(ethylene glycol)-b-poly[N-(2-hydroxypropyl) methacrylamide-dilactate] mPEG-b-p(HPMAm-Lac 2) micelles in order to overcome these drawbacks. It was shown that xanthone could be loaded in these micelles up to 2mg/mL with ∼100% entrapment efficiency and ∼20% loading capacity. The average particle diameter of the xanthone loaded mPEG-b-p(HPMAm-Lac 2) micelles as determined by dynamic light scattering ranged from 84 to 112nm. In vitro assays showed that xanthone in its free form as well as loaded in polymeric micelles had a high cytotoxicity towards both doxorubicin sensitive and, importantly, resistant cancer cells. On the other hand empty mPEG-b-p(HPMAm-Lac 2) micelles did not show any cytotoxicity towards normal cells (PBMCs). Interestingly, the cytostatic effect of xanthone towards normal cells was masked when loaded in the micelles. The mechanism of cell growth inhibition by xanthone-loaded polymeric micelles was mediated through induction of apoptosis, as evidenced from a subdiploid peak of propidium iodide stained cells using flow cytometric analysis. From the results of this study it can be concluded that xanthone has potent anticancer activity not only on sensitive but also on doxorubicin resistant cancer cell lines. mPEG-b-p(HPMAm-Lac 2) micelles are therefore attractive delivery systems of xanthone for the treatment of cancer. © 2012 Elsevier B.V.
format Article
author Khonkarn R.
Mankhetkorn S.
Talelli M.
Hennink W.E.
Okonogi S.
spellingShingle Khonkarn R.
Mankhetkorn S.
Talelli M.
Hennink W.E.
Okonogi S.
Cytostatic effect of xanthone-loaded mPEG-b-p(HPMAm-Lac 2) micelles towards doxorubicin sensitive and resistant cancer cells
author_facet Khonkarn R.
Mankhetkorn S.
Talelli M.
Hennink W.E.
Okonogi S.
author_sort Khonkarn R.
title Cytostatic effect of xanthone-loaded mPEG-b-p(HPMAm-Lac 2) micelles towards doxorubicin sensitive and resistant cancer cells
title_short Cytostatic effect of xanthone-loaded mPEG-b-p(HPMAm-Lac 2) micelles towards doxorubicin sensitive and resistant cancer cells
title_full Cytostatic effect of xanthone-loaded mPEG-b-p(HPMAm-Lac 2) micelles towards doxorubicin sensitive and resistant cancer cells
title_fullStr Cytostatic effect of xanthone-loaded mPEG-b-p(HPMAm-Lac 2) micelles towards doxorubicin sensitive and resistant cancer cells
title_full_unstemmed Cytostatic effect of xanthone-loaded mPEG-b-p(HPMAm-Lac 2) micelles towards doxorubicin sensitive and resistant cancer cells
title_sort cytostatic effect of xanthone-loaded mpeg-b-p(hpmam-lac 2) micelles towards doxorubicin sensitive and resistant cancer cells
publishDate 2014
url http://www.scopus.com/inward/record.url?eid=2-s2.0-84859157763&partnerID=40&md5=ada4a27f53c7906ba838c31e20d957c8
http://cmuir.cmu.ac.th/handle/6653943832/4669
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