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. 2017 Nov 28;22(12):2082.
doi: 10.3390/molecules22122082.

trans-Double Bond-Containing Liposomes as Potential Carriers for Drug Delivery

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Free PMC article

trans-Double Bond-Containing Liposomes as Potential Carriers for Drug Delivery

Giorgia Giacometti et al. Molecules. .
Free PMC article

Abstract

The use of liposomes has been crucial for investigations in biomimetic chemical biology as a membrane model and in medicinal chemistry for drug delivery. Liposomes are made of phospholipids whose biophysical characteristics strongly depend on the type of fatty acid moiety, where natural unsaturated lipids always have the double bond geometry in the cis configuration. The influence of lipid double bond configuration had not been considered so far with respect to the competence of liposomes in delivery. We were interested in evaluating possible changes in the molecular properties induced by the conversion of the double bond from cis to trans geometry. Here we report on the effects of the addition of trans-phospholipids supplied in different amounts to other liposome constituents (cholesterol, neutral phospholipids and cationic surfactants), on the size, ζ-potential and stability of liposomal formulations and on their ability to encapsulate two dyes such as rhodamine B and fluorescein. From a biotechnological point of view, trans-containing liposomes proved to have different characteristics from those containing the cis analogues, and to influence the incorporation and release of the dyes. These results open new perspectives in the use of the unnatural lipid geometry, for the purpose of changing liposome behavior and/or of obtaining molecular interferences, also in view of synergic effects of cell toxicity, especially in antitumoral strategies.

Keywords: cis-trans isomerization; drug-delivery system; liposomes; trans fatty acids; trans-phospholipids.

Conflict of interest statement

The authors declared no conflicts of interest.

Figures

Figure 1
Figure 1
Molecular structures of l-α-phosphatidylcholine (A) and of fatty acid fragments (B); The comparison of oleic acid and elaidic acid structures to evidence the loss of the bent cis geometry (C); Reaction mechanism for the cis-trans isomerization catalyzed by thiyl radicals (D).
Figure 2
Figure 2
Size distribution and ζ-potential of various liposomal formulations (taken from Table 1). Significant differences (p value) are reported as follow: (*) p ≤ 0.05, (**) p ≤ 0.01, (***) p ≤ 0.001, (****) p ≤ 0.0001.
Figure 3
Figure 3
DLS measurements of liposomes at 22 °C (formula image), 37 °C (formula image) and 45 °C (formula image) versus time. (Left panels): POPC formulation A0, B0 and C0; (Right panels): 60-PEPC formulation A60, B60 and C60. The red line shows the size threshold of 200 nm.
Figure 4
Figure 4
Representative AFM images (on the left) and cross-section probles (on the right) of POPC (A) and 60-PEPC (B) liposome acquired with tapping mode as described in Experimental Section.
Figure 5
Figure 5
Effect of the encapsulation technique on the encapsulation efficiency (EE) of rhodamine B in liposomes formulations A0 (white), B0 (grey) and C0 (black). Encapsulation of rhodamine B was carried out by vortexing the suspension for 10 min at 22 °C (Method A), or at 40 °C followed by 2 × 5 min sonication cycles (Method B). The effect of two (Method C) or five (Method D) cycles of freeze-annealing-thaw technique after (Method A) on EE was also tested. Error bars show the differences found in the experiments run in triplicates.
Figure 6
Figure 6
Encapsulation efficiency (EE) of rhodamine B (Left panel) and fluorescein (Right panel) in liposomes formulations A0, B0 and C0, and the corresponding formulations containing 60-PEPC (A60, B60 and C60 respectively). The encapsulation procedure was carried out at 40 °C using two sonication cycles of 5 min each (Method B) and 1:100 dye/lipid ratio. Experiments were run in triplicate. Results are shown as mean EE% ± sd. Significant differences (p value) are reported as follow: (*) p ≤ 0.05, (**) p ≤ 0.01, (***) p ≤ 0.001, (****) p ≤ 0.0001. Differences between cis and trans containing liposomes having the same formulation (black), but also between cis containing formulations (blue) and trans containing formulations (red) are reported.
Figure 7
Figure 7
In vitro release of rhodamine B (Left panel) and fluorescein performed at 37 °C (Right panel). The POPC containing formulations (in black) were compared with the corresponding 60-PEPC containing ones (in red). The release profile of free rhodamine B and free fluorescein (dashed lines) is also reported.

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