On the road to personalized therapy: 3D-printed nanostructured orodispersible films for repurposed anticancer drug delivery in pediatric oncology.

Pediatric cancer treatment is currently challenged by the lack of age-appropriate formulations specifically designed for this population, particularly regarding acceptability, ease of administration, and the need for individualized dosing that accommodates pediatric physiological requirements. The aim of this study was to develop and characterize a three-dimensional (3D)-printed orodispersible film (ODF) using semi-solid extrusion (SSE), intended for the administration of pimavanserin (PIMA) and celecoxib (CXB), selected as repurposed anticancer agents, previously encapsulated in nanostructured lipid carriers (NLCs), for pediatric oncology. The NLCs were selected based on their physicochemical properties, including particle size (PS), polydispersity index (PDI), zeta potential (ZP), and drug content, leading to an optimized NLC formulation exhibiting a particle size of 268 ± 2 nm, a polydispersity index of 0.208, a zeta potential of -2.5 ± 0.1 mV, encapsulation efficiency values of 98.75 ± 0.16% (PIMA) and 99.99 ± 0.01% (CXB) and drug loading values of 2.49 ± 0.08% (PIMA) and 2.47 ± 0.09% (CXB). The ODF polymer matrix, consisting of hydroxypropyl methylcellulose (HPMC), Pluronic® F127, polyvinylpyrrolidone (PVP), glycerol, and polyethylene glycol (PEG400), was selected for its rheological properties suitable for SSE printing, yielding films that met European Pharmacopeia mass uniformity requirements. Among the evaluated process parameters, infill percentage was identified as the critical process parameter governing ODF performance: disintegration time increased from 29 ± 3 s (50% infill) to 45 ± 3 s (100% infill), while swelling index decreased correspondingly (1.415 to 1.132-1.219). Infill density also strongly affected drug release: at 120 min, PIMA release ranged from 44% (100% infill) to over 97% (50% infill), showing that infill modulation alone enables predictable adjustment of dose, disintegration, and release kinetics without altering ink composition. This study reports the first formulation that combines pre-encapsulated PIMA and CXB in NLCs within a 3D-printed ODF using SSE, thereby constituting a promising platform for personalized pediatric drug delivery.