Micro- and nanoencapsulation strategies for mefenamic acid delivery: carrier design, release mechanisms, and preclinical performance

Mefenamic acid, a Biopharmaceutics Classification System (BCS) class II non-steroidal anti-inflammatory drug which is widely used for the treatment of pain and inflammation, but its activity is limited by poor aqueous solubility, rapid metabolism and gastrointestinal toxicity. These constraints increase the first-pass loss, require frequent oral dosing of the drug and reduce bioavailability. We review nanocarrier approaches that enhance dissolution, absorption, and sustained delivery while mitigating the adverse effects. Vesicular systems (niosomes, liposomes, ethosomes) improve encapsulation, targeting, and gastric protection, whereas non-vesicular platforms (self-nanoemulsifying drug delivery systems, nanoemulsions, nanosponges) promote rapid dissolution and uptake. Solid lipid nanoparticles and nanostructured lipid carriers prolong circulation and improve drug retention, and layered double hydroxides and polymeric nanocomposites enable pH-responsive controlled release. Mucoadhesive intranasal nanoemulsions are also discussed for potential nose-to-brain delivery in neuroinflammation. Overall, we appraise pharmacokinetic and therapeutic gains and outline key considerations for clinical translation.