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Comparison of the physical characteristics of Cubosomes prepared using different manufacturing methods

Marta Ruano Aldea

Cubosomes are cubic lyotropic Liquid Crystalline structures consisting of polar lipids, such as glycerol monooleate (GMO) or glycerol monolaurate (GML) that provide the capability of carrying both hydrophilic and lipophilic compounds1-3. The most straightforward method of producing cubic phase particles is the agitation of both phases (oil and water) with a magnetic stirrer resulting in a coarse dispersion. This produces a polydisperse and unstable solution. Further post-manufacture modifications are required to control dispersity and size: ultrasonication5, homogenisation6, and microfluidics7. Aims: The aim of the present study was to formulate cubosomes (see Figure 1)4 in the presence of ethanol (hydrotrope) prepared comparing the three post-manufacture methods. Methods: Three samples were prepared using GMO and GML dissolved in ethanol (oil phase) and the surfactant (F127) dissolved in water (water phase). One sample was sonicated for 5 minutes using 30-40% of the maximum power. The second sample was homogenised for 10 minutes at 8000 rpm. The third sample was prepared using a Neonano device from Neofluidics for 1 minute. The samples were examined by Scanning Electron Microscopy to determine if cubosomes had been formed, and evaluated by Dynamic Light Scattering (DLS) for measurement of particle size and Zeta potential using a Zetasizer Nano ZS90 system to provide a comparison of average droplet size and polydispersity index between all the samples and the measurements of zeta potential showed which method provides better colloidal stability during storage for three months at 4, 25 and 37ºC. Results: The dispersions examined under Scanning Electronic Microscope showed non-aggregated particles confirming the nanoparticle formation for all three methods. The sample produced by microfluidics showed low polydispersity with no variation of the zeta potential over three months. Conclusion: Microfluidics avoids the heat gradient and it reduces the manufacture time with high reproducibility. Acknowledgments: These findings are part of the Knowledge Transfer Partnership (KTP) project developed between AB Vista, Abitec and the University of Strathclyde. The authors would like to express their gratitude to Neofluidics for support in conducting this research.