In this paper, we investigated the behavior of Pickering nano-emulsions stabilized by solid lipid nanoparticles, when administrated by oral route. A first part of the study is dedicated to the characterization and stability studies of solid lipid nanoparticles (SLNs) and SLNs-stabilized Pickering nano-emulsions, against incubation in gastric and intestinal mediums. Characterizations were performed by dynamic light scattering and transmission electron microscopy. The SLNs measured around 40 nm, while the resulting nano-emulsions reached approximately 200 nm with low polydispersity. Transmission electron microscopy confirmed their spherical and homogeneous morphology. Differential scanning calorimetry revealed a thermal transition between 30？C and 40？C, indicating temperature sensitivity suitable for controlled drug release. The second part of the study was related to interactions, cellular uptake, and toxicology of the SLNs-stabilized Pickering nano-emulsions incubated with different cell lines: a healthy cell line MSC-2 and three cancer cell lines A549, U87 and MG-63. This work allows emphasizing the optimal conditions for cellular interactions without toxicity, showing the potential of these lipid Pickering nano-emulsions to be used for therapeutic and diagnostic purposes. In vitro digestion studies showed good stability of the emulsions, even in the presence of digestive enzymes. Cytotoxicity assays on healthy (MSC-2) and cancerous (A549, U87, MG-63) cell lines showed no toxicity at low concentrations. At 1/1000 and 1/10,000 dilutions, cell metabolism was slightly enhanced, suggesting active uptake. Fluorescence imaging confirmed efficient internalization of intact nano-emulsions into cells. These findings highlight the biocompatibility and stability of the system. Overall, the developed Pickering nano-emulsions show strong potential as safe drug delivery carriers.
References
[1]
Bae, Y.H. and Park, K. (2011) Targeted Drug Delivery to Tumors: Myths, Reality and Possibility. Journal of Controlled Release, 153, 198-205. https://doi.org/10.1016/j.jconrel.2011.06.001
[2]
Burrell, R.A. and Swanton, C. (2014) Tumour Heterogeneity and the Evolution of Polyclonal Drug Resistance. Molecular Oncology, 8, 1095-1111. https://doi.org/10.1016/j.molonc.2014.06.005
[3]
Housman, G., Byler, S., Heerboth, S., Lapinska, K., Longacre, M., Snyder, N., et al. (2014) Drug Resistance in Cancer: An Overview. Cancers, 6, 1769-1792. https://doi.org/10.3390/cancers6031769
[4]
Kesharwani, S.S., Kaur, S., Tummala, H. and Sangamwar, A.T. (2018) Overcoming Multiple Drug Resistance in Cancer Using Polymeric Micelles. Expert Opinion on Drug Delivery, 15, 1127-1142. https://doi.org/10.1080/17425247.2018.1537261
[5]
Kitano, H. (2004) Cancer as a Robust System: Implications for Anticancer Therapy. Nature Reviews Cancer, 4, 227-235. https://doi.org/10.1038/nrc1300
[6]
Long, J., Zhang, Y., Yu, X., Yang, J., LeBrun, D.G., Chen, C., et al. (2011) Overcoming Drug Resistance in Pancreatic Cancer. Expert Opinion on Therapeutic Targets, 15, 817-828. https://doi.org/10.1517/14728222.2011.566216
[7]
Markman, J.L., Rekechenetskiy, A., Holler, E. and Ljubimova, J.Y. (2013) Nanomedicine Therapeutic Approaches to Overcome Cancer Drug Resistance. Advanced Drug Delivery Reviews, 65, 1866-1879. https://doi.org/10.1016/j.addr.2013.09.019
[8]
Liu, Q., Das, M., Liu, Y. and Huang, L. (2018) Targeted Drug Delivery to Melanoma. Advanced Drug Delivery Reviews, 127, 208-221. https://doi.org/10.1016/j.addr.2017.09.016
[9]
Ngandeu Neubi, G.M., Opoku-Damoah, Y., Gu, X., Han, Y., Zhou, J. and Ding, Y. (2018) Bio-Inspired Drug Delivery Systems: An Emerging Platform for Targeted Cancer Therapy. Biomaterials Science, 6, 958-973. https://doi.org/10.1039/c8bm00175h
[10]
Oberoi, R.K., Parrish, K.E., Sio, T.T., Mittapalli, R.K., Elmquist, W.F. and Sarkaria, J.N. (2016) Strategies to Improve Delivery of Anticancer Drugs across the Blood-Brain Barrier to Treat Glioblastoma. Neuro-Oncology, 18, 27-36. https://doi.org/10.1093/neuonc/nov164
[11]
Tran, T.T.D. and Tran, P.H.L. (2019) Nanoconjugation and Encapsulation Strategies for Improving Drug Delivery and Therapeutic Efficacy of Poorly Water-Soluble Drugs. Pharmaceutics, 11, Article No. 325. https://doi.org/10.3390/pharmaceutics11070325
[12]
Buruga, K. and Kalathi, J.T. (2019) Synthesis of Poly(styrene-co-methyl methacrylate) Nanospheres by Ultrasound-Mediated Pickering Nanoemulsion Polymerization. Journal of Polymer Research, 26, Article No. 210. https://doi.org/10.1007/s10965-019-1871-9
[13]
Cheong, A.M., Tan, K.W., Tan, C.P. and Nyam, K.L. (2016) Kenaf (Hibiscus cannabinus L.) Seed Oil-in-Water Pickering Nanoemulsions Stabilised by Mixture of Sodium Caseinate, Tween 20 and Β-Cyclodextrin. Food Hydrocolloids, 52, 934-941. https://doi.org/10.1016/j.foodhyd.2015.09.005
[14]
Dieng, S.M., Anton, N., Bouriat, P., Thioune, O., Sy, P.M., Massaddeq, N., et al. (2019) Pickering Nano-Emulsions Stabilized by Solid Lipid Nanoparticles as a Temperature Sensitive Drug Delivery System. Soft Matter, 15, 8164-8174. https://doi.org/10.1039/c9sm01283d
[15]
Sy, P.M., Anton, N., Idoux-Gillet, Y., Dieng, S.M., Messaddeq, N., Ennahar, S., et al. (2018) Pickering Nano-Emulsion as a Nanocarrier for pH-Triggered Drug Release. International Journal of Pharmaceutics, 549, 299-305. https://doi.org/10.1016/j.ijpharm.2018.07.066
[16]
Thompson, K.L., Cinotti, N., Jones, E.R., Mable, C.J., Fowler, P.W. and Armes, S.P. (2017) Bespoke Diblock Copolymer Nanoparticles Enable the Production of Relatively Stable Oil-in-Water Pickering Nanoemulsions. Langmuir, 33, 12616-12623. https://doi.org/10.1021/acs.langmuir.7b02267
[17]
Jiménez Saelices, C. and Capron, I. (2018) Design of Pickering Micro-and Nanoemulsions Based on the Structural Characteristics of Nanocelluloses. Biomacromolecules, 19, 460-469. https://doi.org/10.1021/acs.biomac.7b01564
[18]
Faridi Esfanjani, A. and Jafari, S.M. (2016) Biopolymer Nano-Particles and Natural Nano-Carriers for Nano-Encapsulation of Phenolic Compounds. Colloids and Surfaces B: Biointerfaces, 146, 532-543. https://doi.org/10.1016/j.colsurfb.2016.06.053
[19]
Feng, Y. and Lee, Y. (2016) Surface Modification of Zein Colloidal Particles with Sodium Caseinate to Stabilize Oil-In-Water Pickering Emulsion. Food Hydrocolloids, 56, 292-302. https://doi.org/10.1016/j.foodhyd.2015.12.030
[20]
Jermain, S.V., Brough, C. and Williams, R.O. (2018) Amorphous Solid Dispersions and Nanocrystal Technologies for Poorly Water-Soluble Drug Delivery—An Update. International Journal of Pharmaceutics, 535, 379-392. https://doi.org/10.1016/j.ijpharm.2017.10.051
[21]
Malamatari, M., Somavarapu, S., Taylor, K.M.G. and Buckton, G. (2016) Solidification of Nanosuspensions for the Production of Solid Oral Dosage Forms and Inhalable Dry Powders. Expert Opinion on Drug Delivery, 13, 435-450. https://doi.org/10.1517/17425247.2016.1142524
[22]
Nallamilli, T., Binks, B.P., Mani, E. and Basavaraj, M.G. (2015) Stabilization of Pickering Emulsions with Oppositely Charged Latex Particles: Influence of Various Parameters and Particle Arrangement around Droplets. Langmuir, 31, 11200-11208. https://doi.org/10.1021/acs.langmuir.5b02443
[23]
Tavernier, I., Wijaya, W., Van der Meeren, P., Dewettinck, K. and Patel, A.R. (2016) Food-Grade Particles for Emulsion Stabilization. Trends in Food Science & Technology, 50, 159-174. https://doi.org/10.1016/j.tifs.2016.01.023
[24]
Ramos, G.V.C., Ramírez-López, S., Pinho, S.C.d., Ditchfield, C. and Moraes, I.C.F. (2025) Starch-Based Pickering Emulsions for Bioactive Compound Encapsulation: Production, Properties, and Applications. Processes, 13, Article No. 342. https://doi.org/10.3390/pr13020342
[25]
Guerrero-Vasquez, F.J., Ortega, F., Rubio, R.G. and Guzmán, E. (2025) Bio-Based Interpolyelectrolyte Complexes for the Stabilization of Pickering-Like Emulsions. Colloids and Interfaces, 9, Article No. 9. https://doi.org/10.3390/colloids9010009
[26]
Lobato-Guarnido, I., Luzón, G., Ríos, F. and Fernández-Serrano, M. (2023) Synthesis and Characterization of Environmentally Friendly Chitosan-Arabic Gum Nanoparticles for Encapsulation of Oregano Essential Oil in Pickering Emulsion. Nanomaterials, 13, Article No. 2651. https://doi.org/10.3390/nano13192651
[27]
Pocasap, P., Tamprasit, K., Rungsri, T., Kaimuangpak, K., Srisongkram, T., Katekaew, S., et al. (2024) Pickering Emulsion of Oleoresin from Dipterocarpus Alatus Roxb. Ex G. Don and Its Antiproliferation in Colon (HCT116) and Liver (HepG2) Cancer Cells. Molecules, 29, Article No. 2695. https://doi.org/10.3390/molecules29112695
[28]
Sarkar, A., Goh, K.K.T., Singh, R.P. and Singh, H. (2009) Behaviour of an Oil-in-Water Emulsion Stabilized by β-Lactoglobulin in an in Vitro Gastric Model. Food Hydrocolloids, 23, 1563-1569. https://doi.org/10.1016/j.foodhyd.2008.10.014
[29]
Singh, H., Ye, A. and Horne, D. (2009) Structuring Food Emulsions in the Gastrointestinal Tract to Modify Lipid Digestion. Progress in Lipid Research, 48, 92-100. https://doi.org/10.1016/j.plipres.2008.12.001
[30]
Attia, M.F., Dieng, S.M., Collot, M., Klymchenko, A.S., Bouillot, C., Serra, C.A., et al. (2017) Functionalizing Nanoemulsions with Carboxylates: Impact on the Biodistribution and Pharmacokinetics in Mice. Macromolecular Bioscience, 17, Article ID: 1600471. https://doi.org/10.1002/mabi.201600471
[31]
Klymchenko, A.S., Roger, E., Anton, N., Anton, H., Shulov, I., Vermot, J., et al. (2012) Highly Lipophilic Fluorescent Dyes in Nano-Emulsions: Towards Bright Non-Leaking Nano-Droplets. RSC Advances, 2, 11876-11886. https://doi.org/10.1039/c2ra21544f
[32]
Bouchaala, R., Mercier, L., Andreiuk, B., Mély, Y., Vandamme, T., Anton, N., et al. (2016) Integrity of Lipid Nanocarriers in Bloodstream and Tumor Quantified by Near-Infrared Ratiometric FRET Imaging in Living Mice. Journal of Controlled Release, 236, 57-67. https://doi.org/10.1016/j.jconrel.2016.06.027
[33]
Kilin, V.N., Anton, H., Anton, N., Steed, E., Vermot, J., Vandamme, T.F., et al. (2014) Counterion-Enhanced Cyanine Dye Loading into Lipid Nano-Droplets for Single-Particle Tracking in Zebrafish. Biomaterials, 35, 4950-4957. https://doi.org/10.1016/j.biomaterials.2014.02.053
