Chitosan-Grafted-Poly(N-vinylcaprolactam)-Decorated Fe₃O₄@SiO₂ Core–Shell Nanoformulation as an Efficient Drug Delivery System for Poorly Soluble Drugs

Hydrocortisone, a commonly used anti-inflammatory drug, has limited aqueous solubility and several side effects. To address this challenge, as a proof-of-concept, this article demonstrates the development of a controlled-release drug delivery system (DDS) for hydrocortisone using chitosan-grafted poly( N -vinylcaprolactam) (CS- g -PNVCL)-coated core–shell Fe 3 O 4 @SiO 2 nanoformulations (NFs). Reported magnetic nanoparticles (NPs) were synthesized and modified with silica, PNVCL, and CS precursors to enhance the biocompatibility of DDS and drug-loading efficiency. The release rate of hydrocortisone from Fe 3 O 4 @SiO 2 @CS- g -PNVCL NFs was observed to be higher at lower pH values, and the smart polymer coating demonstrated temperature responsiveness, facilitating drug release at higher temperatures. Fe 3 O 4 @SiO 2 @CS- g -PNVCL NFs exhibited a cell viability of around 97.2 to 87.3% (5–100 μg/mL) after 24–48 h, while the hydrocortisone-NFs had a cell viability of around 93.2 to 82.3%. Our findings suggest that CS- g -PNVCL-coated Fe 3 O 4 @SiO 2 NPs effectively enhance the solubility, loading capacity, and targeted delivery of poorly soluble drugs, thereby improving their therapeutic efficacy and bioavailability.