Despite the impressive characteristics of biological metal organic frameworks (bioMOFs) for their use as drug delivery systems (DDs), there are still some parameters related to their structural stability and processing routes that have decelerated their realistic application in this field. Both drawbacks are unraveled in this work for the microporous bioMOF CaSyr-1 by using supercritical CO₂ (scCO₂) to load the bioMOF with the anti-tubercular isoniazid (INH) drug, and functionalize its external surface with a hydrophobic protective layer of stearate (S). The hydrophobicized CaSyr-1(INH)/S vehicle is further coated with a neutral surfactant (PS60) to enhance the wettability of the system. In vitro tests, related to drug carrier biocompatibility and drug release in body simulated fluids, are performed to demonstrate potential prospective of the designed DDs in pharmacy. The synthetized product displayed total biocompatibility even at high concentrations, and the particle size and dissolution rate showed to be adequate for pulmonary administration.