Inhibition of 3-D tumor spheroids by timed-released hydrophilic and hydrophobic drugs from multilayered polymeric microparticles

First-line cancer chemotherapy necessitates high parenteral dosage and repeated dosing of a combination of drugs over a prolonged period. Current commercially available chemotherapeutic agents, such as Doxil and Taxol, are only capable of delivering single drug in a bolus dose. The aim of this study...

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Main Authors: Tan, Ern Yu, Loo, Say Chye Joachim, Lee, Wei Li, Guo, Wei Mei, Ho, Vincent H. B., Saha, Amitaksha, Chong, Han Chung, Tan, Nguan Soon, Widjaja, Effendi
Other Authors: School of Materials Science & Engineering
Format: Journal Article
Language:English
Published: 2014
Subjects:
Online Access:https://hdl.handle.net/10356/103481
http://hdl.handle.net/10220/24526
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author Tan, Ern Yu
Loo, Say Chye Joachim
Lee, Wei Li
Guo, Wei Mei
Ho, Vincent H. B.
Saha, Amitaksha
Chong, Han Chung
Tan, Nguan Soon
Widjaja, Effendi
author2 School of Materials Science & Engineering
author_facet School of Materials Science & Engineering
Tan, Ern Yu
Loo, Say Chye Joachim
Lee, Wei Li
Guo, Wei Mei
Ho, Vincent H. B.
Saha, Amitaksha
Chong, Han Chung
Tan, Nguan Soon
Widjaja, Effendi
author_sort Tan, Ern Yu
collection NTU
description First-line cancer chemotherapy necessitates high parenteral dosage and repeated dosing of a combination of drugs over a prolonged period. Current commercially available chemotherapeutic agents, such as Doxil and Taxol, are only capable of delivering single drug in a bolus dose. The aim of this study is to develop dual-drug-loaded, multilayered microparticles and to investigate their antitumor efficacy compared with single-drug-loaded particles. Results show hydrophilic doxorubicin HCl (DOX) and hydrophobic paclitaxel (PTX) localized in the poly(dl-lactic-co-glycolic acid, 50:50) (PLGA) shell and in the poly(l-lactic acid) (PLLA) core, respectively. The introduction of poly[(1,6-bis-carboxyphenoxy) hexane] (PCPH) into PLGA/PLLA microparticles causes PTX to be localized in the PLLA and PCPH mid-layers, whereas DOX is found in both the PLGA shell and core. PLGA/PLLA/PCPH microparticles with denser shells allow better control of DOX release. A delayed release of PTX is observed with the addition of PCPH. Three-dimensional MCF-7 spheroid studies demonstrate that controlled co-delivery of DOX and PTX from multilayered microparticles produces a greater reduction in spheroid growth rate compared with single-drug-loaded particles. This study provides mechanistic insights into how distinctive structure of multilayered microparticles can be designed to modulate the release profiles of anticancer drugs, and how co-delivery can potentially provide better antitumor response.
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spelling ntu-10356/1034812020-06-01T10:13:47Z Inhibition of 3-D tumor spheroids by timed-released hydrophilic and hydrophobic drugs from multilayered polymeric microparticles Tan, Ern Yu Loo, Say Chye Joachim Lee, Wei Li Guo, Wei Mei Ho, Vincent H. B. Saha, Amitaksha Chong, Han Chung Tan, Nguan Soon Widjaja, Effendi School of Materials Science & Engineering School of Biological Sciences DRNTU::Science::Biological sciences First-line cancer chemotherapy necessitates high parenteral dosage and repeated dosing of a combination of drugs over a prolonged period. Current commercially available chemotherapeutic agents, such as Doxil and Taxol, are only capable of delivering single drug in a bolus dose. The aim of this study is to develop dual-drug-loaded, multilayered microparticles and to investigate their antitumor efficacy compared with single-drug-loaded particles. Results show hydrophilic doxorubicin HCl (DOX) and hydrophobic paclitaxel (PTX) localized in the poly(dl-lactic-co-glycolic acid, 50:50) (PLGA) shell and in the poly(l-lactic acid) (PLLA) core, respectively. The introduction of poly[(1,6-bis-carboxyphenoxy) hexane] (PCPH) into PLGA/PLLA microparticles causes PTX to be localized in the PLLA and PCPH mid-layers, whereas DOX is found in both the PLGA shell and core. PLGA/PLLA/PCPH microparticles with denser shells allow better control of DOX release. A delayed release of PTX is observed with the addition of PCPH. Three-dimensional MCF-7 spheroid studies demonstrate that controlled co-delivery of DOX and PTX from multilayered microparticles produces a greater reduction in spheroid growth rate compared with single-drug-loaded particles. This study provides mechanistic insights into how distinctive structure of multilayered microparticles can be designed to modulate the release profiles of anticancer drugs, and how co-delivery can potentially provide better antitumor response. ASTAR (Agency for Sci., Tech. and Research, S’pore) 2014-12-22T09:09:53Z 2019-12-06T21:13:36Z 2014-12-22T09:09:53Z 2019-12-06T21:13:36Z 2014 2014 Journal Article Lee, W. L., Guo, W. M., Ho, V. H. B., Saha, A., Chong, H. C., Tan, N. S., et al. (2014). Inhibition of 3-D tumor spheroids by timed-released hydrophilic and hydrophobic drugs from multilayered polymeric microparticles. Small, 10(19), 3986-3996. 1613-6810 https://hdl.handle.net/10356/103481 http://hdl.handle.net/10220/24526 10.1002/smll.201400536 en Small © 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.
spellingShingle DRNTU::Science::Biological sciences
Tan, Ern Yu
Loo, Say Chye Joachim
Lee, Wei Li
Guo, Wei Mei
Ho, Vincent H. B.
Saha, Amitaksha
Chong, Han Chung
Tan, Nguan Soon
Widjaja, Effendi
Inhibition of 3-D tumor spheroids by timed-released hydrophilic and hydrophobic drugs from multilayered polymeric microparticles
title Inhibition of 3-D tumor spheroids by timed-released hydrophilic and hydrophobic drugs from multilayered polymeric microparticles
title_full Inhibition of 3-D tumor spheroids by timed-released hydrophilic and hydrophobic drugs from multilayered polymeric microparticles
title_fullStr Inhibition of 3-D tumor spheroids by timed-released hydrophilic and hydrophobic drugs from multilayered polymeric microparticles
title_full_unstemmed Inhibition of 3-D tumor spheroids by timed-released hydrophilic and hydrophobic drugs from multilayered polymeric microparticles
title_short Inhibition of 3-D tumor spheroids by timed-released hydrophilic and hydrophobic drugs from multilayered polymeric microparticles
title_sort inhibition of 3 d tumor spheroids by timed released hydrophilic and hydrophobic drugs from multilayered polymeric microparticles
topic DRNTU::Science::Biological sciences
url https://hdl.handle.net/10356/103481
http://hdl.handle.net/10220/24526
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