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Inhibition of 3‐D Tumor Spheroids by Timed‐Released Hydrophilic and Hydrophobic Drugs from Multilayered Polymeric Microparticles
Author(s) -
Lee Wei Li,
Guo Wei Mei,
Ho Vincent H. B.,
Saha Amitaksha,
Chong Han Chung,
Tan Nguan Soon,
Widjaja Effendi,
Tan Ern Yu,
Loo Say Chye Joachim
Publication year - 2014
Publication title -
small
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.785
H-Index - 236
eISSN - 1613-6829
pISSN - 1613-6810
DOI - 10.1002/smll.201400536
Subject(s) - plga , paclitaxel , doxorubicin , spheroid , materials science , drug delivery , drug , microparticle , controlled release , drug carrier , pharmacology , biomedical engineering , biophysics , chemistry , nanotechnology , nanoparticle , chemotherapy , chemical engineering , in vitro , medicine , surgery , biochemistry , engineering , biology
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.