Nanomembrane-driven co-elution and integration of active chemotherapeutic and anti-inflammatory agents

Abstract

Erik Pierstorff1, Dean Ho1,21Departments of Biomedical and Mechanical Engineering, Robert R McCormick School of Engineering and Applied Science; 2Robert H Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Evanston, IL, USAAbstract: The release of therapeutic drugs from the surface of implantable devices is instrumental for the reduction of medical costs and toxicity associated with systemic administration. In this study we demonstrate the triblock copolymer-mediated deposition and release of multiple therapeutics from a single thin film at the air-water interface via Langmuir–Blodgett deposition. The dual drug elution of dexamethasone (Dex) and doxorubicin hydrochloride (Dox) from the thin film is measured by response in the RAW 264.7 murine macrophage cell line. The integrated hydrophilic and hydrophobic components of the polymer structure allows for the creation of hybrids of the copolymer and the hydrophobic Dex and the hydrophilic Dox. Confirmation of drug release and functionality was demonstrated via suppression of the interleukin 6 (IL-6) and tumor necrosis factor alpha (TNFα) inflammatory cytokines (Dex), as well as TUNEL staining and DNA fragmentation analysis (Dox). The inherent biocompatibility of the copolymeric material is further demonstrated by the lack of inflammation and apoptosis induction in cells grown on the copolymer films. Thus a layer-by-layer anchored deposition of an anti-inflammatory and chemotherapeutic functionalized copolymer film is able to localize drug dosage to the surface of a medical device, all with an innate material thickness of 4 nm per layer.Keywords: co-elution, combinatorial therapy, nanomedicine, drug delivery, chemotherapy, inflammation