**4. Conclusions**

A feasibility study was conducted to investigate the possibility of developing a green multifunctional device for wound healing applications. Two multifunctional drug delivery systems based on nanostructured ZnO were prepared by means of non-toxic and organic-solvent free procedures.

The antimicrobial properties of the ZnO carriers were investigated against both Gram-positive and Gram-negative bacterial strains, such as *S. aureus* and *K. pneumoniae*, as well as against *C. albicans*. As a whole, the results indicated that the two ZnO nanostructures exhibited the following activity: *S. aureus* > *C. albicans > K. pneumoniae*.

Moreover, an in vitro Zn2+ release study was carried out. A correlation between the antimicrobial activity, the physico–chemical properties (specific surface area and crystal size) of nanostructured ZnO and the Zn2+ ion release was found.

For the first time ibuprofen was successfully loaded on the nanostructured ZnO carriers with a supercritical CO2-mediated drug impregnation process. The drug-loaded amount was observed to depend on the specific surface area and the pore volume of the carrier and up to 14% *w*/*w* of ibuprofen in its amorphous form was obtained inside the final drug delivery system. 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 nanostructured ZnO as a multifunctional antimicrobial drug carrier.

**Supplementary Materials:** The following are available online at http://www.mdpi.com/2079-4991/9/3/407/ s1, Figure S1: Section A: TG curves of NsZnO-1 and IBU@NsZnO-1; Section B: TG curves of NsZnO-2 and IBU@NsZnO-2.

**Author Contributions:** Conceptualization, F.L. and B.O.; Investigation, F.L., R.C. (Roberta Cataldo), S.S.Y.M., S.R., and N.M.; Methodology, L.M., M.B., and N.M.; Resources, L.M., R.C. (Roberta Cavalli), and B.O.; Supervision, B.O.; Validation, L.M., S.R., V.T., and R.C. (Roberta Cavalli); Writing—original draft, F.L. and M.B.; Writing—review and editing, S.S.Y.M., M.B., V.T., and B.O.

**Funding:** This research received no external funding.

**Conflicts of Interest:** The authors declare no conflict of interest.
