Objectives: To prepare and characterize the nanoparticle-based topical formulations of dexibuprofen in combination with calendula oil to enhance the topical anti-inflammatory effect. Methods: Chitosan and tri poly phosphate (TPP) were used to prepare nanoparticles developed utilizing the ionotropic gelation technique and analyzed by scanning electron microscope (SEM) and the ZS. Solvent casting was used to prepare the transdermal medication delivery system for the chitosan nanoparticle formulation. Results: Results revealed that nanoparticles were between the sizes of 267.3 nm. This particle size may enhance the drug’s solubility and penetration through the skin. These patches containing chitosan nanoparticles were produced utilizing polymer combinations - HPMC, chitosan, and PEG400 with tween80 as plasticizers. Accompanying the rise in hydrophilic polymer content came an increase in the rate of medication release via the patch. Conclusion: Transdermal patch - F3 released the drug reasonably well.