Self-Adjusting Biochemically Controlled Nanoparticles - A Strategy to Achieve Precision Therapeutics

Abstract

Drugs such as DMARDs (Disease-Modifying Anti-Rheumatic Drugs), NSAIDs (Non-Steroidal Anti-Inflammatory Drugs), and glucocorticoids are used to manage acute inflammations and flares in chronic diseases, but their long-term use may result in side effects or drug tolerance. To address this, a drug delivery system was developed implementing polymeric nanoparticles (NPs). Although a conventional method such as nanoprecipitation was utilized, a microfluidic system was also established and optimized to evaluate its potential as a formulation technique. Dextran was chosen as a polymer base for its exceptional biocompatibility, biodegradability, and non-toxicity. Its acetalization provided a pH-responsive polymer that was utilized in the formulation of nanoparticles. The pH sensitivity of these nanoparticles was exploited, as inflamed tissues are associated with low pH levels, which led to the degradation of the nanoparticles and to a controlled release of the drug. The drug delivery system exhibited a lower release of the model drug at pH 7.4 than at pH 6.5 and 6.0, with the latter showing significantly higher release over time. Additionally, the drug delivery system displayed self-adjusting properties, as the release of the cargo could be initiated or stopped by altering the pH of NPs-containing buffers (ON/OFF/ON System). Nanoprecipitation enabled the formulation of a drug delivery system with controlled release and self-adjusting properties. This research highlighted the need for additional investigation to fully exploit the potential of the microfluidic system. The NPs offer alternative approaches to treat chronic inflammation diseases, as opposed to conventional therapies.