## 3 In Vivo Applications of MIP-Based DDS
### Drug Reservoirs
Nanostructured DDS based on carbon nanotubes (CNTs) have also taken the spotlight recently. CNTs consist of hexagonal arrangements of carbon atoms, resulting in cylindrical nanostatructures. Based on the layer of graphene sheets, CNTs fall into two categories: single-walled (SWCNTs), with the outer diameter of 0.4-2 nm, and multi-walled CNTs (MWCNTs), with the outer diameter ranging between 10 and 100 nm. CNTs are defined by special distinctive electrical, mechanical and optical characteristics. They are able to bind biological molecules due to their high surface area. Their inner hollow structure is usually used to load certain drugs, while the outer surface can be chemically or physically modified by adsorption, electrostatic interactions or covalent bonds to increase their hydrophilicity [31]. One concern regarding the use of CNTs in living organisms is their significant toxicity observed in vivo conditions, due to their hydrophobic surface and limited solubility in aqueous media. CNTs are considered responsible for many harmful effects, such as free radicals and reactive oxygen species (ROS) formation, apoptosis, and inflammatory effects. To overcome this limitation, CNTs should be functionalized (such as 9-vinylanthracene, 9-VA) to enhance their clearance and thus lower their toxicity [31; 32]. CNTs advantages include: increased surface area, lightness, thermal stability, lack of swelling and high stability in acidic media. They can be associated with LC for oral floating drug reservoirs, with metal-organic framework (MOF) gels for facile dispersion, or even fabricated in binary green porogen systems to avoid the health hazards of conventional solvents [32; 33; 34]. [PERSON] et al. designed a floating device based on MWCNTs, coated with LC-MIPs for the oral delivery of levofloxacin. To bypass the potential safety threats, the nanotubes were functionalized with 9-VA to enhance their clearance. MIP synthesis was based on the \"graffing to\" approach, relying on strong non-covalent bonds which occur at the surface of MIPs due to the \(\pi\)-\(\pi\) interactions of vinyl groups. In vivo pharmacokinetic studies revealed an increased floating time of more than 24 h, along with an impressive relative BA of 578.9%, advising in favor of their potential future applicability in the field of gastro-retentive DDS [20]. MOFs selected for designing MIP-based drug reservoirs offered superior release profiles. MOFs, also known as coordination polymers, are metallic organic frameworks in which metal ions (Cr\({}^{3+}\), Fe\({}^{3+}\)) are bound together by organic ligands (e.g., polycarboxylic acids). The resulting nanostructured materials have a few unique properties, such as high porosity, conductivity, catalytic activity, alongside the possibility to be molecularly imprinted. These distinctive characteristics have brought MOGs significant attention from the research community, as they find applications in various fields [34]. In one study, Fe (III)-trimesic acid was selected as the dispersant for MIP-based DDS, doped with MWCNTs, aiming at the controlled release of aminoglutimide (AG) in breast carcinoma therapy. Preliminary tests revealed a significant increase in the NPs' specific area and pore volume, due to the contribution effect of MWCNTs and MOGs, offering proper porosity and stability to the gels. Interestingly, it was observed that MIP-based MOGs lost their recognition ability after metal ions removal. In vitro and in vivo studies confirmed that MIPs affinity towards the template can be significantly improved by including both MWCNTs and MOGs in the formulation, which are responsible for the enhanced adsorption, controlled release and superior BA of the desired drug [34]. Room temperature ionic liquids (RTILs) are a class of solvents with impressive features. They can act as porogenic agents in the polymerization process and lower MIPs shrinkage in conventional porogens, due to their low vapor pressure.