¹Department of Pharmaceutics, Krupanidhi College of Pharmacy, Bangalore, 560035, Karnataka India DOI : 10.29228/jrp.2024.00 Antiretroviral medication tenofovir disoproxil fumarate (TDF) is frequently used to treat HIV and Hepatitis B virus infection and possesses low oral bioavailability due to low cellular penetration, and intestinal degradation. The present research focuses to develop nanoparticle-loaded oral film of TDF for the pediatric population with an aim to improve bioavailability and patient compliance. A high-shear homogenization process was employed to prepare nanostructured lipid carriers (NLCs) of TDF using an I-Optimal design. The consequences of proportions of solid and liquid lipid, and surfactant concentrations on drug entrapment, loading, and particle size were studied with a planned 14 experimental runs. The optimized formulation was loaded into an oromucosal film using hydroxy propyl methyl cellulose (HPMC) polymer. The films were evaluated for their physicochemical, and mechanical properties. The permeation of the drug from the films through goat oral mucosa was estimated. The design yielded an optimized product characterized by its nanosized (215 nm), stability (0.1 mV), and high entrapment (95.6%) of TDF in the carrier matrix. The surface morphology proved the irregular surface of the nano lipid carrier. The oro-mucosal film exhibited prolonged residence time and was released gradually over 24 h. The permeation of the drug from the nanocarriers loaded film was significantly improved compared to the pure drug. These findings support the idea that NLC-loaded oro-mucosal adhesive films may represent a promising strategy for increasing TDF's oral bioavailability. Keywords : Tenofovir Disoproxil Fumarate; Nano lipid carriers; High shear homogenization; Oro mucosal adhesive film; Solvent Casting method