Sterically stabilized liposomes containing gentamicin: limitations to gentamicin encapsulation

As sterically stabilized liposomes (SSL) containing the aminoglycoside gent amicin prepared by the method of passive loading are characterized by a low drug to lipid ratio, we attempted to prepare gentamicin containing SSL wit h a more efficient encapsulation. Passive loading of a dried lipid film (PE G-DSPE:PHEPC: cholesterol = 0.15:1.85:1.0) with a solution containing 125 m g gentamicin per 250 mu mole lipid yielded liposomes with an encapsulation efficiency of 4.0 +/- 0.4% and a gentamicin loading of 28.0 +/- 0.7 mu g ge ntamicin/mu mole lipid. Encapsulation efficiency was calculated as the perc entage of gentamicin incorporated into liposomes relative to the initial to tal amount of gentamicin in solution and gentamicin loading was calculated as the amount of gentamicin incorporated in liposomes relative to the conte nt of total lipid. Active loading of gentamicin into preformed liposomes which exhibit a trans membrane pH gradient resulted in a lower encapsulation efficiency and genta micin loading (0.4 +/- 0.1% and 4.3 +/- 1.2 mu g/mu mole, respectively). Ad dition of calcium ions to the hydration buffer did not alter the encapsulat ion efficiency nor the gentamicin loading in both loading strategies. In co nclusion, it seems that the encapsulation efficiency for gentamicin in SSL with the lipid composition PEG-DSPE, PHEPC and cholesterol (in a molar rati o 0.15: 1.85: 1.0) is limited to 4%, or 28 mu g gentamicin per mu mole lipi d. The preparation method to achieve this encapsulation is the passive load ing of liposomes with gentamicin.