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Recent developments in porous coordination polymers make them attractive candidates for various potential applications including systems for controlled drug administration. Drug delivery systems based on metal–organic frameworks (MOF) are usually constructed either by non-covalent adsorption of drug molecules inside the pores of the material or by covalent modification of organic linkers. Herein, we propose alternative method for incorporation of drug molecules inside MOFs by binding them to the metal node using Solvent-Assisted Ligand Incorporation (SALI). We tested NU-1000 platform which contains 8-connecting Zr6-nodes, which can bind up to 4 carboxylate-based ligands. Using SALI technique we successfully anchored three model drug molecules containing carboxylate groups: ketoprofen, nalidixic acid and levofloxacin with drug loadings reaching 30 wt% yielding guest@NU-1000 materials. Our study shows that NU-1000 is stable in phosphate concentrations present in blood plasma, whereas drug molecules can be released from guest@NU-1000 under these conditions without decomposition of the MOF framework. We also observed that the drug release kinetics strongly depends on the size of the guest molecules.