Preparation, characterization, and application of silica nanoparticles and silica aerogel in smart drug delivery systems

• Advanced surface modification enhances drug loading & biocompatibility. • PH/ROS-responsive release targets infections, doubles efficacy vs MDR pathogens. • Fights antimicrobial resistance in chronic infections like MDR-TB. • Addresses scalability and regulatory paths for clinical translation. • Compares silica nanocarriers favorably to lipid/polymeric systems. Silica nanoparticles (SNPs) and silica aerogels (SAs) have emerged as new drug delivery platforms with promise for treating chronic conditions such as multidrug-resistant tuberculosis (MDR-TB) and diabetic foot infections. This review integrates papers from 2015 to 2025, selected by PubMed and Scopus searches through the use of keywords like ’silica nanoparticles drug delivery chronic infections’ to detect its significance in the fight against AMR with a maximum of 50 % enhanced drug loading efficiency. Because of their tunable porosity and favorable biocompatibility, nanoparticulate and aerogel materials are well compatible with target and controlled release of drugs, and this is how it is possible to bypass complications caused by poor drug penetration and microbial resistance. This review article, for the first time, addresses the application of silica nanoparticles and aerogels to fight drug-resistant infections in terms of scalability as well as regulatory considerations. With respect to scalability as well as regulatory, including the 2025 horizon scanning report of EMA on nanomedicines for enhanced biocompatibility and GMP scalability. It also addresses recent advances in surface modification techniques, such as covalent grafting of amine groups and non-covalent coating with polymers such as chitosan. These alterations have increased the drug loading capability (approximately 30 to 50 wt% for antibiotics) and have facilitated stimulus-responsive drug release triggered by stimuli including pH change and reactive oxygen species (ROS). The data from this review indicate that nanocarrier surface optimization has a significant ability to enhance therapeutic efficacy, wherein antibacterial action against drug-resistant microbes is increased two-fold. This review is distinct from previous structural-focused reviews because it investigates the direct relationship between drug loading capacity and surface modifications and smart drug release. Its focus on chronic drug-resistant infection renders the review an imperative reference document for guiding subsequent studies and generating clinical applications.