In Situ Gel Based Smart Drug Delivery Systems: Chemical Insights and Application in Diabetes

Stimuli-responsive in situ gel-based smart drug delivery systems represent an innovative
approach to diabetes therapy that addresses the limitations of conventional formulations,
such as poor bioavailability, short drug half-life, and frequent dosing. These systems undergo
sol-to-gel transitions in response to physiological stimuli, including pH, temperature, ions,
and enzymatic activity, enabling controlled and prolonged drug release. Synthetic polymers
such as poloxamers, poly (ethylene glycol) (PEG) derivatives, and poly(Nisopropylacrylamide) (PNIPAAm) allow the precise modulation of gelation behavior, stability,
and physicochemical properties. Due to their biocompatibility and stimuli-responsiveness, in
situ gels have been explored via oral, nasal, ocular, injectable, and transdermal routes for the
delivery of insulin, oral hypoglycemics, and peptide-based drugs. Recent advances have
integrated nanoparticles and glucose-sensitive components for feedback-regulated insulin
release, closely mimicking pancreatic β-cell function, and improving therapeutic precision.
Despite challenges, such as limited mechanical strength, gelation variability, and regulatory
constraints, continued progress in polymer chemistry, nanotechnology, and biomaterial
design is expected to overcome these barriers. Collectively, the in-situ gel-based delivery
systems offer a promising, patient-friendly, and physiologically adaptive platform for nextgeneration diabetes management.