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Supercritical solvent impregnation (SSI) is a green unconventional technique for preparing amorphous drug formulations. A mesoporous nanostructured ZnO (mesoNsZnO) carrier with 8-nm pores, spherical-nanoparticle morphology, and an SSA of 75 m2/g has been synthesized and, for the first time, subjected to SSI with poorly water-soluble drugs. Ibuprofen (IBU), clotrimazole (CTZ), and hydrocortisone (HC) were selected as highly, moderately, and poorly CO2-soluble drugs. Powder X-ray diffraction, Fourier transform infrared spectroscopy, field emission scanning electron microscopy, nitrogen adsorption analysis, and ethanol extraction coupled with ultraviolet spectroscopy were employed to characterize the samples and quantify drug loading. Successful results were obtained with IBU and CTZ while HC loading was negligible, which could be related to different solubilities in CO2, drug size, and polarity. Successful SSI resulted in amorphous multilayer confinement of the drug. The mesoNsZnO-IBU system showed double drug loading than the mesoNsZnO-CTZ one, with a maximum uptake of 0.24 g/g. Variation of contact time during SSI of the mesoNsZnO-IBU system showed that drug loading triplicated between 3 and 8 h with an additional 30% increment between 8 h and 24 h. SSI did not affect the mesoNsZnO structure, and the presence of the adsorbed drug reduced the chemisorption of CO2 on the carrier surface.

The physico–chemical and biological properties of nanostructured ZnO are combined with the non-toxic and eco-friendly features of the scCO2-mediated drug loading technique to develop a multifunctional antimicrobial drug delivery system for potential applications in wound healing. Two nanostructured ZnO (NsZnO) with different morphologies were prepared through wet organic-solvent-free processes and characterized by means of powder X-ray diffraction, field emission scanning electron microscopy (FESEM), and nitrogen adsorption analysis. The antimicrobial activity of the two samples against different microbial strains was investigated together with the in vitro Zn2+ release. The results indicated that the two ZnO nanostructures exhibited the following activity: S. aureus > C. albicans > K. pneumoniae. A correlation between the antimicrobial activity, the physico–chemical properties (specific surface area and crystal size) and the Zn2+ ion release was found. Ibuprofen was, for the first time, loaded on the NsZnO carriers with a supercritical CO2-mediated drug impregnation process and in vitro dissolution studies of the loaded drug were performed. A successful loading up to 14% w/w of ibuprofen in its amorphous form was obtained. A preliminary drug release test showed that up to 68% of the loaded ibuprofen could be delivered to a biological medium, confirming the feasibility of using NsZnO as a multifunctional antimicrobial drug carrier.