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Effective Delivery of Arsenic Trioxide to HPV-Positive Cervical Cancer Cells Using Optimised Liposomes: A Size and Charge Study

Despite the success of arsenic trioxide (ATO) in treating haematological malignancies, its potential to treat solid tumours has not been fully exploited, owing to its dose-limiting toxicity and poor pharmacokinetics. In order to overcome this hurdle, liposomal encapsulation of the drug with differen...

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Autores principales: Akhtar, Anam, Wang, Scarlet Xiaoyan, Ghali, Lucy, Bell, Celia, Wen, Xuesong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5979440/
https://www.ncbi.nlm.nih.gov/pubmed/29617346
http://dx.doi.org/10.3390/ijms19041081
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author Akhtar, Anam
Wang, Scarlet Xiaoyan
Ghali, Lucy
Bell, Celia
Wen, Xuesong
author_facet Akhtar, Anam
Wang, Scarlet Xiaoyan
Ghali, Lucy
Bell, Celia
Wen, Xuesong
author_sort Akhtar, Anam
collection PubMed
description Despite the success of arsenic trioxide (ATO) in treating haematological malignancies, its potential to treat solid tumours has not been fully exploited, owing to its dose-limiting toxicity and poor pharmacokinetics. In order to overcome this hurdle, liposomal encapsulation of the drug with different surface charges (neutral, negative, and positive) and sizes (100, 200 and 400 nm) were synthesised and tested on human papilloma virus (HPV)-positive HeLa and HPV-negative HT-3 cervical cancer cell lines. Two epithelial cell lines—human keratinocytes (HK) and human colon cells (CRL-1790)—were used as controls. The synthesised liposomes were tested for their physico-chemical characteristics, drug loading efficiency, and toxicity on the studied cell lines. Neutral liposomes of 100 nm in size were the chosen formulation for delivering ATO into the studied cells, as they showed the least intrinsic cytotoxicity and the highest loading efficiency. The findings demonstrated that the optimised formulation of liposomes was an effective drug delivery method for HPV-infected cervical cancer cells. Furthermore, the toxicity vs. uptake ratio was highest for HeLa cells, while a reduced or minimal toxic effect was observed for non-HPV-infected cervical cancer cells and control cells. These findings may provide a promising therapeutic strategy for effectively managing cervical cancers.
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spelling pubmed-59794402018-06-10 Effective Delivery of Arsenic Trioxide to HPV-Positive Cervical Cancer Cells Using Optimised Liposomes: A Size and Charge Study Akhtar, Anam Wang, Scarlet Xiaoyan Ghali, Lucy Bell, Celia Wen, Xuesong Int J Mol Sci Article Despite the success of arsenic trioxide (ATO) in treating haematological malignancies, its potential to treat solid tumours has not been fully exploited, owing to its dose-limiting toxicity and poor pharmacokinetics. In order to overcome this hurdle, liposomal encapsulation of the drug with different surface charges (neutral, negative, and positive) and sizes (100, 200 and 400 nm) were synthesised and tested on human papilloma virus (HPV)-positive HeLa and HPV-negative HT-3 cervical cancer cell lines. Two epithelial cell lines—human keratinocytes (HK) and human colon cells (CRL-1790)—were used as controls. The synthesised liposomes were tested for their physico-chemical characteristics, drug loading efficiency, and toxicity on the studied cell lines. Neutral liposomes of 100 nm in size were the chosen formulation for delivering ATO into the studied cells, as they showed the least intrinsic cytotoxicity and the highest loading efficiency. The findings demonstrated that the optimised formulation of liposomes was an effective drug delivery method for HPV-infected cervical cancer cells. Furthermore, the toxicity vs. uptake ratio was highest for HeLa cells, while a reduced or minimal toxic effect was observed for non-HPV-infected cervical cancer cells and control cells. These findings may provide a promising therapeutic strategy for effectively managing cervical cancers. MDPI 2018-04-04 /pmc/articles/PMC5979440/ /pubmed/29617346 http://dx.doi.org/10.3390/ijms19041081 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
Akhtar, Anam
Wang, Scarlet Xiaoyan
Ghali, Lucy
Bell, Celia
Wen, Xuesong
Effective Delivery of Arsenic Trioxide to HPV-Positive Cervical Cancer Cells Using Optimised Liposomes: A Size and Charge Study
title Effective Delivery of Arsenic Trioxide to HPV-Positive Cervical Cancer Cells Using Optimised Liposomes: A Size and Charge Study
title_full Effective Delivery of Arsenic Trioxide to HPV-Positive Cervical Cancer Cells Using Optimised Liposomes: A Size and Charge Study
title_fullStr Effective Delivery of Arsenic Trioxide to HPV-Positive Cervical Cancer Cells Using Optimised Liposomes: A Size and Charge Study
title_full_unstemmed Effective Delivery of Arsenic Trioxide to HPV-Positive Cervical Cancer Cells Using Optimised Liposomes: A Size and Charge Study
title_short Effective Delivery of Arsenic Trioxide to HPV-Positive Cervical Cancer Cells Using Optimised Liposomes: A Size and Charge Study
title_sort effective delivery of arsenic trioxide to hpv-positive cervical cancer cells using optimised liposomes: a size and charge study
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5979440/
https://www.ncbi.nlm.nih.gov/pubmed/29617346
http://dx.doi.org/10.3390/ijms19041081
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