The effect of aminoglycoside antibiotics on the thermodynamic properties of liposomal vesicles.

Liposomes are ideal drug-delivery systems because they can alter the pharmacokinetic characteristics and biodistribution profile of the incorporated bioactive molecule. The effect of the aminoglycoside antibiotics, gentamicin (GN), tobramycin (TOB), and amikacin (AMI), on the thermodynamic properties of multilamellar vesicles composed of 1,2-dipalmitoyl- sn-glycero-3-phosphocholine (DPPC) was studied by using differential scanning calorimetry (DSC), electron paramagnetic resonance (EPR), and 31P nuclear magnetic resonance (NMR) spectroscopy. The relationship between the structure of aminoglycoside antibiotics and their effect on the physical properties of the liposomal bilayers was investigated. The incorporation of the drugs was achieved and an osmotic gradient created by controlling the mole ratio of the drug inside to that outside of the DPPC vesicles so that [druginside DPPC]/[drugoutside DPPC] was 1:0, 1:0.2, 1:1, or 1:2.5. Incorporation of the drugs into liposomes caused the Tm to shift to a higher temperature and the δHm and δT1/2 values to decrease. The 2Amax and the order parameter (S), obtained from the EPR spectra, indicated that the fluidity of the liposomal membrane was affected by the type of drug and by the concentration used; GN and TOB decreased the fluidity and disturbed chain packing at mole ratios of [druginside DPPC]/[drugoutside DPPC] ranging from 1:0 to 1:0.2, while AMI increased the fluidity and disrupted chain packing at an osmotic gradient of 1:2.5. In conclusion, the molecular organization and thermotropic properties of the multilamellar DPPC vesicles were dependent on the osmotic gradient and structure of the aminoglycoside. [ABSTRACT FROM AUTHOR]