**5. Conclusions**

As a general principle, the in situ formation of liposomes from a combination of phospholipids and porous carriers in the simulated GI conditions is an effective approach for formulating liposomes for oral delivery. We propose that a single-step loading of phospholipids and drug substances can be used as a simple and effective method for the production of proliposomal formulations. This method is suitable for scale-up. We showed the mechanism of the spontaneous in situ formation of liposomes in different dissolution media and demonstrated drug encapsulation in the emerging liposomes. To enhance the encapsulation efficiency and reduce drug leakage from the liposomes, other types of phospholipids and their combinations with amphiphilic polymers can be used with porous microparticulate carriers, such as FCC.

**Supplementary Materials:** The following are available online at http://www.mdpi.com/1999-4923/12/8/777/s1, Figure S1: Cryo-EM images of liposomes. Figure S2: Differential scanning calorimeter (DSC) spectra of the formulations and physical mixture. Table S1: The time required for 80% of the drug content to dissolve in SGF. Video S1: Formation of liposomes in SGF.

**Author Contributions:** M.F.: conceptualization, methodology, formal analysis, investigation, writing—original draft, visualization. G.Q.: conceptualization, methodology, investigation, writing—review and editing, funding acquisition. K.S.: methodology, investigation. F.M.H.: writing—review and editing, resources, funding acquisition. J.S.: writing—review and editing, resources, funding acquisition. J.H.: conceptualization, resources, writing—review and editing, supervision, funding acquisition. M.P.: conceptualization, formal analysis, writing—review and editing, supervision, project administration, funding acquisition. All authors have read and agreed to the published version of the manuscript.

**Funding:** This research was co-funded by Omya International AG and Phospholipid Research Center.

**Acknowledgments:** We express deep gratitude to Darryl Borland for his remarkable job regarding technical support of the experimental set ups and for proofreading the manuscript, as well as Peter van Hoogevest for the helpful discussions throughout the execution of the project and for the valuable comments on the manuscript.

**Conflicts of Interest:** The authors declare the following financial interests/personal relationships that may be considered as potential competing interests: two of the authors (F.H. and J.S.) are employees of Omya International AG, the supplier of the material used in this study. Omya International AG had no role in the design of the study; in the collection, analyses or interpretation of data; in the writing of the manuscript, nor in the decision to publish the results. Other authors declare no conflict of interest.
