Stimuli-responsive local drug molecule delivery to adhered cells in a 3D nanocomposite scaffold

Drug delivery systems capable of providing controlled and localized drug release are a highly important tool in the biomedical field because they can provide site-specific, sustained, and controlled drug release at the place where the drug is most needed, and they allow for significantly lower doses of the drug at other parts of the body, reducing the drug’s potential side effects. In this respect, we describe pH-responsive PMO/alginate nanocomposite (NC) scaffolds with different pH-responsive strengths for controlled local drug delivery applications. To prepare the PMO/alginate NC scaffolds, PMOs were first loaded with anti-cancer molecules and then coated with a non-biopolymer or a biopolymer, after which the PMOs were embedded into an alginate network. We found that drug release from the PMOs was regulated by the pH of the environment and the surface coating of the PMOs due to the different pHdependent levels of electrostatic interactions between all the charged components of the NC scaffolds. The non-biopolymer-coated formulation of the NC scaffold can be utilized to deliver higher dosages of drug molecules directly to cells, while the biopolymer-coated system is useful for slow and prolonged release of drugs and for enhanced cell adhesion. Nonetheless, both systems can be utilized, in particular, to deliver higher dosages of drug molecules directly to cancer cells while delivering less of the drug to healthy cells.