| Autor: |
Erensoy G; Division of Chemical Biology, Department of Life Sciences, Chalmers University of Technology, Gothenburg 412 96, Sweden., Råberg L; Division of Chemical Biology, Department of Life Sciences, Chalmers University of Technology, Gothenburg 412 96, Sweden., von Mentzer U; Division of Chemical Biology, Department of Life Sciences, Chalmers University of Technology, Gothenburg 412 96, Sweden., Menges LD; Division of Chemical Biology, Department of Life Sciences, Chalmers University of Technology, Gothenburg 412 96, Sweden., Bardhi E; Division of Chemical Biology, Department of Life Sciences, Chalmers University of Technology, Gothenburg 412 96, Sweden., Hultgård Ekwall AK; The Rheumatology Clinic, Sahlgrenska University Hospital, Gothenburg 413 45, Sweden.; Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg 413 46, Sweden., Stubelius A; Division of Chemical Biology, Department of Life Sciences, Chalmers University of Technology, Gothenburg 412 96, Sweden. |
| Abstrakt: |
Polymer-based nanoparticles (NPs) that react to altered physiological characteristics have the potential to enhance the delivery of therapeutics to a specific area. These materials can utilize biochemical triggers, such as low pH, which is prone to happen locally in an inflammatory microenvironment due to increased cellular activity. This reduced pH is neutralized when inflammation subsides. For precise delivery of therapeutics to match this dynamic reaction, drug delivery systems (DDS) need to not only release the drug (ON) but also stop the release (OFF) autonomously. In this study, we use a systematic approach to optimize the composition of acetalated dextran (AcDex) NPs to start (ON) and stop (OFF) releasing model cargo, depending on local pH changes. By mixing ratios of AcDex polymers (mixed NPs), we achieved a highly sensitive material that was able to rapidly release cargo when going from pH 7.4 to pH 6.0. At the same time, the mix also offered a stable composition that enabled a rapid ON/OFF/ON/OFF switching within this narrow pH range in only 90 min. These mixed NPs were also sensitive to biological pH changes, with increased release in the presence of inflammatory cells compared to healthy cells. Such precise and controllable characteristics of a DDS position mixed NPs as a potential treatment platform to inhibit disease flare-ups, reducing both systemic and local side effects to offer a superior treatment option for inflammation compared to conventional systems. |
