Dual drug delivery of tamoxifen and quercetin: Regulated metabolism for anticancer treatment with nanosponges.

Lockhart JN, Stevens DM, Beezer DB, Kravitz A, Harth E
J Control Release. 2015 220 (Pt B): 751-7

PMID: 26344396 · DOI:10.1016/j.jconrel.2015.08.052

We report the synthesis and encapsulation of polyester nanosponge particles (NPs) co-loaded with tamoxifen (TAM) and quercetin (QT) to investigate the loading, release and in vitro metabolism of a dual drug formulation. The NPs are made in two variations, 4% and 8% crosslinking densities, to evaluate the effects on metabolism and release kinetics. The NP-4% formulation with a particle size of 89.3 ± 14.8 nm was found to have loading percentages of 6.91 ± 0.13% TAM and 7.72 ± 0.15% QT after targeting 10% (w/w) each. The NP-8% formulation with a particle size of 91.5 ± 9.8 nm was found to have loading percentages of 7.26 ± 0.10% TAM and 7.80 ± 0.12% QT. The stability of the formulation was established in simulated gastrointestinal fluids, and the metabolism of TAM was shown to be reduced 2-fold and 3-fold for NP-4%s and NP-8%s, respectively, while QT metabolism was reduced 3 and 4-fold. The implications for improved bioavailability of the NP formulations were supported by cytotoxicity results that showed a similar efficacy to free dual drug formulations and even enhanced anti-cancer effects in the recovery condition. This work demonstrates the suitability of the nanosponges not only as a dual release drug delivery system but also enabling a regulated metabolism through the capacity of a nanonetwork. The variation in crosslinking enables a dual release with tailored release kinetics and suggests improved bioavailability aided by a reduced metabolism.

Copyright © 2015 Elsevier B.V. All rights reserved.

MeSH Terms (27)

Animals Antineoplastic Combined Chemotherapy Protocols Biological Availability Biotransformation Breast Neoplasms Cell Line, Tumor Cell Survival Chemistry, Pharmaceutical Cross-Linking Reagents Cytochrome P-450 CYP3A Delayed-Action Preparations Dose-Response Relationship, Drug Drug Carriers Drug Stability Female Gastric Juice Glucuronosyltransferase Intestinal Secretions Kinetics Mice Nanomedicine Nanoparticles Particle Size Polyesters Quercetin Solubility Tamoxifen

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