Non-steroidal anti-inflammatory drugs (NSAIDs) are one of the most prescribed drugs for pain and inflammatory treatment around the world [1]. These drugs are highly effective as painkillers, anti-inflammatories, and antipyretics. They are essential to treat various conditions, including arthritis, post-surgery pain, musculoskeletal disorders, and wound healing [[2], [3], [4], [5], [6], [7], [8]]. NSAIDs inhibit the cyclooxygenase 1 and 2 (COX1 and COX2), which induces inflammation through the synthesis of prostaglandins and other pro-inflammatory compounds derived from arachidonic acid [9,10]. However, the NSAIDs inhibition of COX1 and COX2 is non-selective, which combined with prolonged administration due to easy access to these drugs, can produce different systemic problems such as kidney toxicity [11,12], gastric toxicity [13,14], liver toxicity [15,16], and cardiac malfunction, in between others [17]. Additionally, NSAIDs have low water solubility that reduces their adsorption and bioavailability, requiring high and repetitive doses to produce their therapeutic actions. Therefore, as mentioned, due to the side effects and the dosage problems of NSAIDs, innovative administration methods are required to reduce the risk associated with these drugs [18].

Drug delivery systems (DDS) are devices developed to overcome the limitations related to the administration route, low solubility, and low bioavailability of drugs [19,20]. In the last decades, the most used DDS are metallic nanoparticles (AgO NP, ZnO NP, or Au NP), polymeric nanoparticles (nanospheres, dendrimer, or nanocapsules), or lipidic nanoparticles (liposomes, vesicles, micelles, and solid lipid NP) [21,22]. The selection of a DDS is defined by the drug, the target tissue, and the selected therapeutic strategy. In this sense, the use of metallic NP has been widely studied in the literature, due to the NP capacity of being employed in diagnosing and treating pathologies simultaneously, referred to as theragnostic applications [23,24]. These studies highlight metal-organic frameworks (MOFs) due to their potential applications as DDS and theragnostic systems. MOFs are a subfamily of porous coordination polymers (PCP) first described by Yaghi et al. in 1995 [25,26]. MOF structure can be divided into a metallic cluster or secondary building units (SBU) and an organic bridging molecule (linker). The SBU corresponds to a tridimensional unit formed by metallic ions coordinated with oxygen or nitrogen atoms, which are the most commonly used. The linker interconnects the SBUs, creating a three-dimensional array characteristic for MOFs [27]. Due to its composition, all MOF show high porosity, modulable flexibility, high surface area, large surface-to-volume ratio, and good thermal, mechanical, and physicochemical stability [28]. Among the different reported MOF, UiO-66, is recognized for its large surface area, and high thermal and water stabilities. [29] Furthermore, UiO-66 has shown the capability to carry different drugs, thus acting as a DDS. Thus, UiO-66 has been employed as an antitumor drug carrier of doxorubicin (DOX) [30], curcumin [31], and imatinib [32]. However, few studies have been focused on the UiO-66 application as a DDS for NSAIDs [33]. As DDS, most studies have been carried out using ibuprofen, which is used as a model for non-soluble NSAIDs [34,35]. On the other hand, the adsorption of some NSAIDs, such as ibuprofen, naproxen, and diclofenac, on UiO-66 has been reported to purify wasted water [[36], [37], [38]]. Nevertheless, there is no reported systematic and comparative study to understand the adsorption and release process of NSAIDs using UiO-66 as DDS. In this work, a complete characterization of the adsorption process using a theoretical and an experimental approach is presented to characterize the intake and release of ibuprofen, naproxen and diclofenac. Thus, DFT calculations were performed over a model of the SBU interacting with the three NSAIDs. Furthermore, the adsorption model and release kinetics were studied for UiO-66. Finally, MOFs have also been studied in biology as a DDS, specifically for wound healing [8,[39], [40], [41], [42]], which is a multi-step process. One of the crucial steps for wound healing is to control the inflammatory stage to avoid a prolonged healing period and risk of infection [40]. Therefore, the viability test in vitro in endothelial cells (EC) was conducted, which are affected during the inflammatory process of wound healing, [39,43], and the NSAIDs delivery effect in an in vitro model of wound closure with a monolayer of EC was studied.