The effect of liposomal charge on the distrubution of liposomes to the liver, brain, lungs and kidneys in a rat model

English:Gentamicin was selected out of three drugs as the most appropriate liposomal marker based on its properties There after, a simple method for preparation of charged Iiposomes by rotary evaporation and hydration was adopted. Surface charge was induced by varying the lipid composition whereby neutral liposomes were prepared using phosphatidyl choline and cholesterol (9.7:6.9, molar ratio), negative and positive liposomes were prepared by addition of dieetyl phosphate (5: I :0.5, molar ratio) and stearylamine (5: I :0.5, molar ratio) to the neutral liposomes, respectively. The distribution of the encapsulated gentamicin to the specified organs in liposome treated groups was compared to a control group treated with free gentamicin at the following intervals: 1, 2, 4, 6 and 8 hours post injection. Gentamicin (60 mg/kg) free and liposome entrapped was administered intraperitoneally and five rats of each group were utilised at each time interval. Under ether anaesthesia, a blood sample was drawn and the relevant organs were harvested. The sodium hydroxide digestion method was used to extract gentamicin from the organs, and gentamicin in plasma and organ extracts was measured by fluorescence polarisation immunoassay. Liposomal characterisation revealed multilammelar Iiposomes with a mean internal diameter of 3.17 ± 1.9 urn, and encapsulation efficiency greater than 15 %. In the animal studies, liposomes delayed elimination of the encapsulated drug. The half life was 2.02 ± 0.5, 1.76 ± 0.1 and 2.04 ± 0.3 hours for the negative, positive and neutral liposome treated groups, respectively, . versus 1.53 ± 0.02 hours for the control group. Peak plasma gentamicin concentrations were higher with positive liposomes than negative and neutral liposomes at 1 hour, while the negative Iiposomes depicted a sustained release pattern between 4 and 8 hours. Distribution of liposomes to the brain and liver was dependent on liposomal surface charge. Liposomes improved gentamicin concentrations in the brain with positive liposomes highest in this regard. A biphasic pattern of distribution to the brain, with lowest gentamicin concentration at 4 hours was observed in the three liposome groups, and this was more marked in the negative liposome group. Generally, hepatic gentamicin concentrations were higher with liposomes than the control. Although, the average hepatic gentamicin concentrations were highest for positive liposomes, the negative liposomes were preferred for the liver because the concentrations were more consistent and increased with time. Uptake of gentamicin by the lungs was not enhanced by liposomes and was independent of surface charge of the liposomes. Renal concentrations of gentamicin were lower (3 to 5 folds) with liposomes, and uptake was not charge dependent. In conclusion, a simple method for preparation of liposomes was adopted. The distribution studies suggested that positively charged liposomes had highest affinity for the brain and the negative liposomes for the liver. Also, liposomes irrespective of charge exhibited reduced renal concentration of gentamicin.