This research highlights the capacity of a newly introduced centrifugation process to form liposomes from water-in-fluorocarbon nano-emulsions stabilized with phospholipids to incorporate macromolecular and sensitive active pharmaceutical ingredients (API). The encapsulation efficiency of the produced liposomes, incorporating fluorescein-sodium, bovine serum albumin and fluorecein isothiocyanate dextran as model APIs, is determined by applying Vivaspin^® centrifugation filtration and quantified by UV-Vis spectroscopy. It was found that higher densities of the fluorocarbons used as the hydrophobic phase enable a higher encapsulation efficiency and that an efficiency of up to 98% is possible depending on the used phospholipid. Among the engineering aspects of the process, a comparison between different membrane substances was performed. Efficiency increases with a higher phospholipid concentration but decreases with the addition of cholesterol. Due to the higher bending modulus, liposome formation is slowed down by cholesterol during liposome closure leading to a greater leakage of the model API. The encapsulation of bovine serum albumin and dextran, both investigated under different osmotic conditions, shows that an efflux negatively affects the encapsulation efficiency while an influx increases the stability. Overall, the process shows the potential for a very high encapsulation efficiency for macromolecules and future pharmaceutical applications.

Fluorocarbons are novel systems in the fast-growing fields of diverse biomedical applications and fluorocarbon-water emulsions. However, characterization of these systems with modern measuring techniques such as drop profile analysis tensiometry is almost impossible because of practically identical refractive indexes and high-density differences. Due to the material properties of the fluorocarbon-water system, the invasive Du Noüy ring is the most appropriate method to measure interfacial tensions over long times. However, the influence of the ring on a fluorocarbon/water interface packed with phospholipids needs careful analysis. For the proof of methodology, the spinning drop tensiometry was used for comparison as a non-invasive technique to measure interfacial tension between water and perfluoroperhydrophenanthrene (PFPH) covered by 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC) proving almost identical results. This demonstrates the validity of the invasive measurement technique for the studied system. The Du Noüy ring method was applied for further measurements of phospholipids with different chain lengths (1,2-dmyristoyl-sn-glycero-3-phostphatidylcholine, DMPC; 1,2-distearoyl-sn-glycero-3-phosphatidylcholine, DSPC) which revealed a difference in interfacial adsorption kinetics and equilibrium tensions. The Du Noüy ring tensiometry is appropriate to examine the slow adsorption kinetics of phospholipids emulsifying fluorocarbons. The results enable functional optimization of fluorocarbon emulsions regarding physical emulsification parameters and the selection of lipids.

Fluorocarbons are one of the most promising hydrophobic phases for future pharmaceutical production processes and various biomedical applications. Yet, because of their specific characteristics such as high density and refractive index similar to water, analysis of water‐in‐fluorocarbon (w/fc) nanoemulsions remains a challenge. The present work examines w/fc nanoemulsions stabilized with phospholipids as natural emulsifiers and tackles the measuring problems of photon correlation spectroscopy (PCS) when used for investigation of fluorocarbon nanoemulsions. These emulsions are suitable to form liposomes via centrifugation and thus, are required to meet certain criteria such as stability and size. The results imply a stability of up to 4 weeks with an average size of 180 nm. The intensity mean diameter gained from PCS measurements shows large scattering directly after sonication which is due to gas bubbles from sonication. The number mean is not influenced by gas bubbles and gives a more accurate depiction of the produced nanoemulsions. These findings are supported by small‐angle X‐ray scattering data, which are additionally applied for liposome analysis measuring a size of approximately 60 nm.

Phospholipids (PLs) are widely used in the pharma industry and a better understanding of their behavior under different conditions is helpful for applications such as their use as medical transporters. The transition temperature T_m affects the lipid conformation and the interfacial tension between perfluoroperhydrophenanthrene (PFP) and an aqueous suspension of 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC), 1,2-distearoyl-sn-glycero-3-phosphatidylcholine (DSPC), as well as a mixture of these PLs with cholesterol. Interfacial tensions were measured with the Du Noüy ring at quasi-equilibrium; the area per molecule was calculated according to the Gibbsian approach and a time-dependent tension gradient. Results show that the time t_ε to reach quasi-equilibrium was shorter when the temperature was above T_m, indicating a faster adsorption process (t_ε,DPPC,_{36 °C} = 48 h, t_{ε,DPPC,48 °C} = 24 h) for PL in the liquid crystalline state than in the gel state (T < T_m). In addition, concentration-dependent results of the interfacial tension revealed that above the respective T_m and at all concentrations c > 0.1 mM, the average minimum interfacial tension for DPPC and DSPC (14.1 mN/m and 15.3 mN/m) does not differ significantly between those two lipids. Equilibrium between monolayers and bilayers shows that for T < T_m, surface pressures ∏ ≈ 31 mN/m are reached while for T > T_m, ∏ ≈ 41 mN/m. Mixtures with cholesterol only reach ∏ ≤ 31 mN/m T_m, with no significant difference between the two PLs. The higher interfacial tension of the mixture indicates stabilization of the liposomal conformation in the aqueous phase by the addition of cholesterol. The high diffusion coefficients show that adsorption is mainly based on liposomes.