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

Connections (1)

This publication is referenced by other Labnodes entities: