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

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 anticancer 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. (C) 2015 Elsevier B.V. All rights reserved.