**4. Conclusions**

In the present paper, we demonstrated the successful application of a new technological lipid-based delivery matrix (Lipomatrix) able to protect lipophilic plant-derived active principles from the gastric compartment and favoring the formation of hydro-dispersible forms in the duodenum, thanks to the pH-dependent ionization of ASP. Lipomatrix-based formulation, despite the not improved apparent bioaccessibility data, seems to enhance overall enteric absorption of SRO in a CACO-2 cells model and this data well correlates with an overall improvement of its biologic effects on in vitro prostatic tissue model, compared to not formulated commercial SRO. Indeed, we showed that the Lipomatrix-associated fraction of SRO reduced inflammation and modulated cytokines pattern expression, enhanced pro-apoptotic caspases-mediated activity and improved myo-relaxation significantly better than not formulated SRO contained in the mentioned commercial products. Lipomatrix-associated SRO shoved furthermore to significantly reduce PSA expression in *LNCaP* prostatic cells but not better than one of the two SRO-containing commercial formulations tested. Moreover, even though as preliminary evidence, SRO formulated in Lipomatrix seems to ensure a higher safety profile on in vitro intestinal model in terms of overall cell vitality, compared to the tested commercial formulations.

To conclude, taken together the data collected in this work, it is possible to consider Lipomatrix as a promising, next generation technological platform for improving enteric delivery of SRO and as consequence its efficacy on human prostatic gland, so confirming the potential significant role of delivery systems in bioavailability of natural lipophilic compounds.

#### **Supplementary Materials:** Supplementary materials can be found at http://www.mdpi.com/1422-0067/20/3/ 669/s1.

**Author Contributions:** Conceptualization, A.F.; methodology, A.F., V.M., F.B., E.T., E.M.; software, F.B., E.T.; validation, V.M., F.B.; formal analysis, M.P.; investigation, A.F., V.M., F.B., E.T., E.M.; resources, S.V.; data curation V.M., F.B., E.T.; writing—original draft preparation, A.F., V.M., F.B., E.T.; writing—review and editing A.F., V.M., F.B., E.T., M.P.; visualization, A.F., M.P.; supervision A.F.G.C., F.B.; project administration, S.V.

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

**Acknowledgments:** This work was mainly funded and supported by PHF SA, Lugano, Swiss. We are grateful to Prof. Stefano Dall'Acqua, Prof. Alessandra Semenzato, Dr. Marta Faggian, Dr. Elisa Barbieri, and Dr. Alessia Costantini, UNIRED, Department of Pharmaceutical and Pharmacological Sciences of Padova University, for the valuable and competent analytical support provided during the described experiments.

**Conflicts of Interest:** A.F., V.M., and M.P. are employees of LABOMAR SRL, the company owner of the patented Lipomatrix technology.
