Amphiphilic pH-responsive core-shell nanoparticles can increase the performances of cellulose-based drug delivery systems.

Polymer and nanoparticles (NPs) together are able to form nanocomposite materials that combine the beneficial properties of the traditional single systems. In this work, we propose a stimuli-responsive nanocomposite system which combines pH-responsive NPs with cellulose. Ring opening polymerization (ROP) followed by two reversible addition-fragmentation chain transfer (RAFT) polymerization steps were performed to synthetize ((PHEMA-graft-LA)-co-PMAA)-b-PDEGMA copolymer characterized by tailored molecular weights and low polydispersity values. Uniform NPs were obtained by nanoprecipitation of the so-obtained copolymer in water. Moreover, drug release studies (using rhodamine b, fluorescein isothiocyanate, pyrene and 5-fluorouracil) at different pHs demonstrated the pH-responsivity of NPs, revealing a significant improvement of hydrophobic molecules release at acidic conditions. In vitro tests verified the biocompatibility of NPs and the efficacy in decreasing cancer cell viability. Finally, NPs were loaded into hydroxypropylmethyl-cellulose-C matrix to obtain the final polymer-NPs composite system. The composite systems showed the ability to sustain the release of low steric hindrance drugs loaded with NPs and high steric hindrance ones loaded within the polymeric network. Overall, the proposed pH-responsive drug delivery system represents a co-delivery device which could be applied for localized treatment in different combined therapeutic program.