**4. Conclusions**

Enhanced penetration of B12 through the skin is possible using the lipid vesicle formulations (L1, T2d, and T1d) designed in this work, which opens the possibility to improve the clinical results obtained in previous studies and to investigate its utility for topical treatment of atopic dermatitis and psoriasis. Several particle properties such as size, stability, and purification method were revealed as key parameters to achieve a suitable and efficient production of lipid vesicles. Skin permeability studies should be further investigated to elucidate if these nanosystems are able not only to increase the penetration in the skin but also to allow the passage of B12 to the systemic circulation, thus broadening the possible applications of the systems for the treatment of other pathologies related with B12 deficiencies.

**Supplementary Materials:** The following are available online at https://www.mdpi.com/1999-4 923/13/3/418/s1, Figure S1: Release parameters (10 and 72 h) for release kinetic models: Higuchi, Korsmeyer–Peppas, Kim, Peppas–Sahlin, zero order, and first order; Figure S2: *R* <sup>2</sup> values of Korsmeyer–Peppas and first order models for the B12 vesicles release data (10 and 72 h).

**Author Contributions:** Conceptualization, A.J.G., E.J.-M., T.M.G., and A.M.; methodology, A.J.G., T.M.G., and A.M.; software, A.J.G.; formal analysis, A.J.G., T.M.G., and A.M.; investigation and visualization, A.J.G., N.L., E.J.-M., and C.M.-G.; resources, M.C.M. and A.M.; writing—original draft preparation, A.J.G.; writing—review and editing, A.M., T.M.G., and M.C.M.; supervision, M.C.M., T.M.G., and A.M.; funding acquisition, M.C.M. and A.M. All authors have read and agreed to the published version of the manuscript.

**Funding:** A.J.G acknowledges the support of the "Atracció de Talent" fellowship of the University of Valencia (grant UV-INV-PREDOC-18F2-743816). A.J.G., T.M.G., and A.M. would also like to thank the University of Valencia and the Valencian Government (grants UV-19-INV-AE19 and GV2015-054). M.C.M., A.J.G., and A.M. acknowledge the Spanish Ministry of Science and Innovation-FEDER (SAF2017-85806-R). All authors acknowledge the support from AIMPLAS (project 3D-Future: IMDEEA/2019/90).

**Institutional Review Board Statement:** Not applicable.

**Informed Consent Statement:** Not applicable.

**Data Availability Statement:** Data is contained within the article.

**Acknowledgments:** All illustrations were created with Biorender.com.

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