Tabriz University of Medical Sciences Advanced Pharmaceutical Bulletin 2228-5881 16 3 2026 09 30 Optimization, Ex-Vivo Penetration and In-Vivo Evaluation of Pegylated Nanostructured Lipid Carriers of Olmesartan Medoxomil to Enhance Transdermal Delivery 524 536 10.34172/apb.46458 EN Rofida Albash https://orcid.org/0000-0003-1775-264X Aly A. Abdelbary Hanan Refai Mohamed A. El-Nabarawi Journal Article 10.34172/apb.46458 2025 09 28 2026 03 20 Introduction: Olmesartan medoxomil (OLM), a poorly water soluble hypertension medication with 26% oral bioavailability, was encapsulated in PEGylated nanostructured lipid carriers (PNLCs) for transdermal distribution. Methods: Tween 80 or sodium deoxycholate stabilized the PNLCs, which were made up of liquid lipid including a mixture of medium chain triglycerides (labrasol and labrafil) and solid lipid (compritol and tristearin). Hot melt emulsification, high-speed stirring, and ultrasonication were used to create PNLCs. To distinguish the effects of formulation independent variables on entrapment efficiency %, particle size, polydispersity index, zeta potential, and amount of drug released after 6 hours (Q6h), a 24 complete factorial design using Design Expert® software was created. Results: For additional research, the formula (PNLC16) with the best requirements was chosen. When compared to OLM solution, PNLC16 showed higher permeation ex vivo permeation using both shed snake and rat skin. Histopathological analysis demonstrated that the topically administered PNLCs were safe. Pharmacodynamic research further demonstrated PNLC16’s superiority over commercial oral pills in terms of long-lasting effects. Conclusion: Accordingly, the results showed that PNLC16 would be a viable vehicle for OLM transdermal delivery.