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Novel Honokiol-eluting PLGA-based scaffold effectively restricts the growth of renal cancer cells
Renal Cell Carcinoma (RCC) often becomes resistant to targeted therapies, and in addition, dose-dependent toxicities limit the effectiveness of therapeutic agents. Therefore, identifying novel drug delivery approaches to achieve optimal dosing of therapeutic agents can be beneficial in managing toxi...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7746163/ https://www.ncbi.nlm.nih.gov/pubmed/33332399 http://dx.doi.org/10.1371/journal.pone.0243837 |
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author | Hamedani, Yasaman Chakraborty, Samik Sabarwal, Akash Pal, Soumitro Bhowmick, Sankha Balan, Murugabaskar |
author_facet | Hamedani, Yasaman Chakraborty, Samik Sabarwal, Akash Pal, Soumitro Bhowmick, Sankha Balan, Murugabaskar |
author_sort | Hamedani, Yasaman |
collection | PubMed |
description | Renal Cell Carcinoma (RCC) often becomes resistant to targeted therapies, and in addition, dose-dependent toxicities limit the effectiveness of therapeutic agents. Therefore, identifying novel drug delivery approaches to achieve optimal dosing of therapeutic agents can be beneficial in managing toxicities and to attain optimal therapeutic effects. Previously, we have demonstrated that Honokiol, a natural compound with potent anti-tumorigenic and anti-inflammatory effects, can induce cancer cell apoptosis and inhibit the growth of renal tumors in vivo. In cancer treatment, implant-based drug delivery systems can be used for gradual and sustained delivery of therapeutic agents like Honokiol to minimize systemic toxicity. Electrospun polymeric fibrous scaffolds are ideal candidates to be used as drug implants due to their favorable morphological properties such as high surface to volume ratio, flexibility and ease of fabrication. In this study, we fabricated Honokiol-loaded Poly(lactide-co-glycolide) (PLGA) electrospun scaffolds; and evaluated their structural characterization and biological activity. Proton nuclear magnetic resonance data proved the existence of Honokiol in the drug loaded polymeric scaffolds. The release kinetics showed that only 24% of the loaded Honokiol were released in 24hr, suggesting that sustained delivery of Honokiol is feasible. We calculated the cumulative concentration of the Honokiol released from the scaffold in 24hr; and the extent of renal cancer cell apoptosis induced with the released Honokiol is similar to an equivalent concentration of direct application of Honokiol. Also, Honokiol-loaded scaffolds placed directly in renal cell culture inhibited renal cancer cell proliferation and migration. Together, we demonstrate that Honokiol delivered through electrospun PLGA-based scaffolds is effective in inhibiting the growth of renal cancer cells; and our data necessitates further in vivo studies to explore the potential of sustained release of therapeutic agents-loaded electrospun scaffolds in the treatment of RCC and other cancer types. |
format | Online Article Text |
id | pubmed-7746163 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-77461632020-12-31 Novel Honokiol-eluting PLGA-based scaffold effectively restricts the growth of renal cancer cells Hamedani, Yasaman Chakraborty, Samik Sabarwal, Akash Pal, Soumitro Bhowmick, Sankha Balan, Murugabaskar PLoS One Research Article Renal Cell Carcinoma (RCC) often becomes resistant to targeted therapies, and in addition, dose-dependent toxicities limit the effectiveness of therapeutic agents. Therefore, identifying novel drug delivery approaches to achieve optimal dosing of therapeutic agents can be beneficial in managing toxicities and to attain optimal therapeutic effects. Previously, we have demonstrated that Honokiol, a natural compound with potent anti-tumorigenic and anti-inflammatory effects, can induce cancer cell apoptosis and inhibit the growth of renal tumors in vivo. In cancer treatment, implant-based drug delivery systems can be used for gradual and sustained delivery of therapeutic agents like Honokiol to minimize systemic toxicity. Electrospun polymeric fibrous scaffolds are ideal candidates to be used as drug implants due to their favorable morphological properties such as high surface to volume ratio, flexibility and ease of fabrication. In this study, we fabricated Honokiol-loaded Poly(lactide-co-glycolide) (PLGA) electrospun scaffolds; and evaluated their structural characterization and biological activity. Proton nuclear magnetic resonance data proved the existence of Honokiol in the drug loaded polymeric scaffolds. The release kinetics showed that only 24% of the loaded Honokiol were released in 24hr, suggesting that sustained delivery of Honokiol is feasible. We calculated the cumulative concentration of the Honokiol released from the scaffold in 24hr; and the extent of renal cancer cell apoptosis induced with the released Honokiol is similar to an equivalent concentration of direct application of Honokiol. Also, Honokiol-loaded scaffolds placed directly in renal cell culture inhibited renal cancer cell proliferation and migration. Together, we demonstrate that Honokiol delivered through electrospun PLGA-based scaffolds is effective in inhibiting the growth of renal cancer cells; and our data necessitates further in vivo studies to explore the potential of sustained release of therapeutic agents-loaded electrospun scaffolds in the treatment of RCC and other cancer types. Public Library of Science 2020-12-17 /pmc/articles/PMC7746163/ /pubmed/33332399 http://dx.doi.org/10.1371/journal.pone.0243837 Text en © 2020 Hamedani et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Hamedani, Yasaman Chakraborty, Samik Sabarwal, Akash Pal, Soumitro Bhowmick, Sankha Balan, Murugabaskar Novel Honokiol-eluting PLGA-based scaffold effectively restricts the growth of renal cancer cells |
title | Novel Honokiol-eluting PLGA-based scaffold effectively restricts the growth of renal cancer cells |
title_full | Novel Honokiol-eluting PLGA-based scaffold effectively restricts the growth of renal cancer cells |
title_fullStr | Novel Honokiol-eluting PLGA-based scaffold effectively restricts the growth of renal cancer cells |
title_full_unstemmed | Novel Honokiol-eluting PLGA-based scaffold effectively restricts the growth of renal cancer cells |
title_short | Novel Honokiol-eluting PLGA-based scaffold effectively restricts the growth of renal cancer cells |
title_sort | novel honokiol-eluting plga-based scaffold effectively restricts the growth of renal cancer cells |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7746163/ https://www.ncbi.nlm.nih.gov/pubmed/33332399 http://dx.doi.org/10.1371/journal.pone.0243837 |
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