Enhanced siRNA delivery with novel smart chitosan-based formulations

This study aims to develop an innovative multifunctional and dual responsive drug formulation for precise siRNA delivery to breast cancer sites, addressing the challenges posed by conventional cancer treatments which often result in adverse side effects due to their non-specific nature. The formulation made by incorporating gold coated superparamagnetic iron oxide nanoparticles (Au-SPIONs) into chitosan microspheres, which were subsequently loaded with siRNA. Comprehensive characterization, including scanning electron microscopy (SEM), transmission electron microscopy (TEM), dynamic light scattering (DLS), Fourier-transform infrared spectroscopy (FTIR), and energy-dispersive X-ray spectroscopy (EDS) confirmed the formulationʼs favourable morphology, particle size distribution, chemical composition, and stability, indicating its strong potential for effective siRNA drug delivery applications. The developed formulation demonstrated siRNA encapsulation efficiencies ranging from 27.4 % to 88.6 % and loading capacity from 0.291 % to 1.59 %, these values particularly higher for medium molecular weight chitosan. These results were compared across different formulations, showing that variations in chitosan type and crosslinker concentration significantly influenced encapsulation efficiency and drug release profiles. Additionally, our results were compared to previous studies on chitosan microspheres encapsulating organic drugs and siRNA, where the developed system demonstrated similar encapsulation and release properties.. The type of chitosan and the choice of crosslinker significantly influenced the drug release patterns. Diverse release profiles across batches highlighted the necessity for precise formulation control. Incorporating SPIONs into chitosan microspheres presents a promising strategy for magnetically driven, site-specific drug delivery. The dual pH-responsive and magnetic properties enable rapid and targeted siRNA release, leveraging the acidic tumor microenvironment as an internal stimulus in addition to external magnetic stimuli. This novel combination of SPIONs, chitosan microspheres, and siRNA encapsulation represents a new approach for targeted drug delivery. While further research is needed to refine and optimize this approach, our study provides a proof of concept for advancing targeted cancer therapies.