title: Inhibition of 3-D tumor spheroids by timed-released hydrophilic and hydrophobic drugs from multilayered polymeric microparticles.
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.
authors.affiliation: School of Materials Science and Engineering, Nanyang Technological University, 50 Nanyang Avenue, 639798, Singapore.
authors.forename: Wei Li
authors.initials: WL
authors.lastname: Lee
authors.forename: Wei Mei
authors.initials: WM
authors.lastname: Guo
authors.forename: Vincent H B
authors.initials: VH
authors.lastname: Ho
authors.forename: Amitaksha
authors.initials: A
authors.lastname: Saha
authors.forename: Han Chung
authors.initials: HC
authors.lastname: Chong
authors.forename: Nguan Soon
authors.initials: NS
authors.lastname: Tan
authors.forename: Effendi
authors.initials: E
authors.lastname: Widjaja
authors.forename: Ern Yu
authors.initials: EY
authors.lastname: Tan
authors.forename: Say Chye Joachim
authors.initials: SC
authors.lastname: Loo
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry; D004317:Doxorubicin / Q000737:chemistry; D016503:Drug Delivery Systems; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D019344:Lactic Acid / Q000737:chemistry; D061986:MCF-7 Cells; D018613:Microscopy, Confocal; D008855:Microscopy, Electron, Scanning; D008863:Microspheres; D049388:Polyanhydrides / Q000737:chemistry; D011091:Polyesters; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000737:chemistry*; D013059:Spectrum Analysis, Raman; D018874:Spheroids, Cellular / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D049388:Polyanhydrides; D011091:Polyesters; D011108:Polymers; C523504:poly(1,6-bis-4-carboxyphenoxyhexane); D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; C033616:poly(lactide); D004317:Doxorubicin
keywords: biodegradable materials; chemotherapy; drug delivery; microparticles; tumor spheroids