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Title: Inhibition of 3-D tumor spheroids by timed-released hydrophilic and hydrophobic drugs from multilayered polymeric microparticles
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
Keywords: DRNTU::Science::Biological sciences
Issue Date: 2014
Source: 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.
Series/Report no.: Small
Abstract: 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.
ISSN: 1613-6810
DOI: 10.1002/smll.201400536
Rights: © 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.
Fulltext Permission: none
Fulltext Availability: No Fulltext
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