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The feasibility of using nanoliposomes as an oral delivery system to improve the intestinal absorption of coenzyme Q(10) (CoQ(10), ubiquinone-10) was examined using Caco-2 cell monolayers as the model of human intestinal epithelium. The apparent permeability coefficient of CoQ(10) with nanoliposomes as vehicles was increased to be 4.19 +/- 0.76 x 10(-6) cm/s, which was higher than the favorable intestinal absorption value (1 x 10(-6) cm/s). The kinetic data demonstrated that nanoliposomal CoQ(10) transport occurred via passive diffusion and carrier mediation routes. Nanoliposomes might suppress the modulation activity of the peptide transporter, organic anion transporter, and P-glycoprotein through fluidizing cell membrane. The transported CoQ(10) was still in the original oxidative form as ubiquinone-10. However, 70-80% of coenzyme Q(10) accumulated by the cells was in the reduced form (ubiquinol-10, CoQ(10)H(2)), suggesting that the conversion of CoQ(10) to CoQ(10)H(2) takes place in the enterocytes during its absorption. These results indicated that the absorption behavior of CoQ(10) was modified through nanoliposomes. The bioavailability of CoQ(10) following its oral administration might be improved with nanoliposomes as the delivery system.

Salidroside liposomes were prepared by using five different methods: thin film evaporation, sonication, reverse phase evaporation, melting, and freezing-thawing. The effect of different preparation methods and salidroside loading capacity on the formation of liposomes and their physicochemical properties were evaluated by means of encapsulating efficiency, particle size, morphology, and zeta potential. Results showed that the encapsulating efficiency of liposomes was highest when prepared by freezing-thawing, followed by thin film evaporation, then reverse phase evaporation and the lowest with melting and sonication. Loading capacity of salidroside had a significant effect on encapsulating efficiency, average diameter, and zeta potential of liposomes. Liposomal systems prepared by sonication, melting, and reverse phase evaporation displayed better dispersivity. Determination of leakage of salidroside from different liposomal systems revealed that the melting method had the lowest leakage of 10% and 15%, at 4 and 30 degrees C after 1 month of storage, respectively. In all cases, a straight-line leakage behavior of salidroside was found. This revealed that the leakage of salidroside was a diffusion process from the membrane of liposomes. Furthermore, the storage stability of different liposomal systems showed that salidroside liposomes prepared by melting had a better physicochemical stability. Instability in the systems was exacerbated when temperature increased. Salidroside liposomes showed the slower increase in particle size than liposomes without salidroside. This could indicate that salidroside played an important role in preventing the aggregation and fusion of liposomes.

Coenzyme Q(10) (CoQ(10)) is incorporated in nanoliposomes composed of egg yolk phospholipid, cholesterol, and Tween 80. Atomic force microscopy, performed to characterize vesicle surface topology, shows some visible influence of CoQ(10) on the nanoliposomal structure. CoQ(10) incorporation can suppress the increase of the z-average diameter of nanoliposomes during storage for 8 months at 4 degrees C. The liposomal lipid peroxidation caused by Fe(III)/ascorbate is also significantly inhibited. Perturbation of acyl chain motion of lipids due to the presence of CoQ(10) in the bilayer is examined by fluorescence probe diphenyl-hexatriene and Raman spectroscopy. Fluorescence probe studies indicate that CoQ(10) incorporation results in the microviscosity increase of nanoliposomes. The steric structure of nanoliposomes reflected by Raman spectroscopy changes obviously and shows CoQ(10) content dependency. The order parameters for the lateral interaction between chains increase. The trans conformation decrease and the gauche conformation increase as the weight contents of CoQ(10) incorporation are at 1%, 5%, 10%, and 32.5%. However, the order parameters for the longitudinal interaction in chains was higher than that of pure nanoliposomes as the weight content of CoQ(10) is at 25%. Results suggest that CoQ(10)might intercalate between lipid molecules and perturb the bilayer structure.

The optimal formulation of coenzyme Q10 (CoQ10) nanoliposomes and the feasibility of production in a pilot scale were investigated. The nanoliposomes were prepared by ethanol injection and sonication techniques for a desired vesicle size in the laboratory. Optimization of formulation in the preparation of CoQ10 nanoliposomes was achieved by an orthogonal array design. The best formulation was found to be phospholipid/CoQ10/cholesterol/Tween 80 (2.5:1.2:0.4:1.8, w/w) with phosphate buffer solution (pH 7.4, 0.01 M) as the hydration media. The z-average diameter (D(z)) was about 68 nm. The encapsulation efficiency was greater than 95% with a retention ratio higher than 90% and a particle size change lower than 10% after storage at 4 degrees C in the dark for 90 days. CoQ10 incorporation resulted in a dramatic increase of the microviscosity of nanoliposomes and inhibited the peroxidation of phospholipid. The D(z) of CoQ10 nanoliposomes produced in a pilot scale was about 67 nm. Results suggest that the technology developed by this investigation is practical to produce the CoQ10 nanoliposomes with the expected encapsulation quality and stability not only in the laboratory but also in a pilot scale.

Abstract: The effects of cholesterol and Tween 80 on the physical stability of empty liposomes were investigated. Results showed that the physical stability of liposomes, including electrostatic and steric stability, was improved by addition of cholesterol and Tween 80. Liposomes prepared by different methods, thin-film hydration, thin-film sonication, reverse-phase evaporation and freeze-thawing, were tested for their capacity to encapsulate ferrous sulfate. Technology parameters to microencapsulate ferrous sulfate, concentration of ferrous sulfate, hydrating media and sonication strength, were optimized. The concentration of ferrous sulfate and the hydrating medium had a significant effect on the amount of encapsulated ferrous ions. The encapsulation efficiency (EE) of 67% was obtained by using the reverse-phase evaporation method. In milk fortified with ferrous sulfate liposomes, the concentration of iron increased to 15 mgL−1, and it was stable to heat sterilization (100 °C, 30 min) and storage at 4 °C during one week. [Copyright &y& Elsevier]