Microfluidic fabrication of dexamethasone-loaded silk fibroin microspheres for targeted pulmonary drug delivery

Abstract

This study developed a microfluidic-based method for the fabrication of dexamethasone-loaded silk fibroin microspheres (SFD), engineered for targeted pulmonary drug delivery. The microfluidic platform, combined with a self-assembly approach, enables green and simple synthesis of microspheres while allowing precise control over microsphere morphology, yielding a uniform aerodynamic diameter of 6.20 ± 0.14 µm and achieved high encapsulation efficiency of 74.46 ± 0.19% with a drug loading capacity of 17.18 ± 0.04%. Kinetic studies demonstrated sustained drug release for over 60 hours in phosphate-buffered saline (PBS), confirming the microspheres’ potential for prolonged therapeutic action. While in vitro cytotoxicity assays showed slightly reduced A549 cell viability (<80%) due to dexamethasone's antiproliferative activity, the SFD exhibited minimal cytotoxicity (>95%) toward RAW264.7 macrophages. Furthermore, in a pro-inflammatory model, the SFD significantly suppressed secretion of key inflammatory cytokines including IL-1β, IL-6, and TNF-α, while minimizing systemic side effects through localized anti-inflammatory activity. This work addresses limitations of traditional pulmonary drug delivery systems by integrating microfluidic precision, controlled release, and targeted delivery into a biocompatible platform. By reducing off-target toxicity and enhancing therapeutic localization, the SFD system represents a transformative strategy for pulmonary inflammation treatment. The findings underscore the potential of microfluidic technologies to revolutionize precision medicine in respiratory therapeutics, with implications for clinical translation and personalized treatment protocols.