**4. Conclusions**

In conclusion, CUR and/or MTX co-loaded PCL/PEG6000 nanocapsules were successfully prepared by interfacial deposition of the pre-formed polymer. Nanometer-sized, monodisperse, amorphous/non-crystalline formulations with high drug-loading efficiencies were obtained. No changes in FTIR assignments were recorded after the nanoencapsulation procedure. In addition, NCUR/MTX-2 provided a statistically significant decrease of Calu-3 cell viability by MTT and SRB assays even at low concentrations of these chemotherapeutic agents. A synergistic effect was proven by the use of this co-loaded nanocarrier. The fluorescence-morphological analysis revealed a cell death pattern based on early and late apoptosis. No necrotic cell was observed in the Calu-3 cells after treating with the co-loaded formulation NCUR/MTX-2. In summary, the co-loaded nanocapsules method can be further used as a novel therapeutic strategy by intravenous or pulmonary route for treating non-small-cell lung cancer to hold the potential for achieving therapeutic outcomes while reducing the incidence of adverse drug effects.

**Author Contributions:** Preparation and Characterization of nanoparticles, L.A.C.R., P.V.F., J.M.N. and A.N.; Encapsulation Efficiency analyses, A.L., F.M.B. and T.K.; Microscopy analyses, Manuscript writing, J.M.B.; In vitro Drug Release study, P.V.F., J.M.N., M.C.B. and A.D.L.; In vitro Cell Culture-based assays, L.A.C.R., P.V.F., M.C.B. and C.C.K.; Statistical analysis, P.V.F. and S.M.W.Z.; Insights on Discussion topics, English editing, V.R.; Supervision of the Laboratory work, S.M.W.Z. All authors have read and agreed to the published version of the manuscript.

**Funding:** This research was funded by CNPq—Conselho Nacional de Pesquisa e Desenvolvimento, grant number 313704/2019-8.

**Acknowledgments:** The authors are grateful to CLABMU-UEPG for technical support.

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