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

[摘要] English:Gentamicin was selected out of three drugs as the most appropriate liposomal marker basedon its properties There after, a simple method for preparation of charged Iiposomes by rotaryevaporation and hydration was adopted. Surface charge was induced by varying the lipidcomposition whereby neutral liposomes were prepared using phosphatidyl choline andcholesterol (9.7:6.9, molar ratio), negative and positive liposomes were prepared by additionof dieetyl phosphate (5: I :0.5, molar ratio) and stearylamine (5: I :0.5, molar ratio) to theneutral liposomes, respectively. The distribution of the encapsulated gentamicin to thespecified organs in liposome treated groups was compared to a control group treated withfree 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 ofeach group were utilised at each time interval. Under ether anaesthesia, a blood sample wasdrawn and the relevant organs were harvested. The sodium hydroxide digestion method wasused to extract gentamicin from the organs, and gentamicin in plasma and organ extracts wasmeasured by fluorescence polarisation immunoassay.Liposomal characterisation revealed multilammelar Iiposomes with a mean internal diameterof 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 gentamicinconcentrations were higher with positive liposomes than negative and neutral liposomes at 1hour, while the negative Iiposomes depicted a sustained release pattern between 4 and 8hours. Distribution of liposomes to the brain and liver was dependent on liposomal surface charge.Liposomes improved gentamicin concentrations in the brain with positive liposomes highestin this regard. A biphasic pattern of distribution to the brain, with lowest gentamicinconcentration at 4 hours was observed in the three liposome groups, and this was more marked in the negative liposome group. Generally, hepatic gentamicin concentrations werehigher with liposomes than the control. Although, the average hepatic gentamicinconcentrations were highest for positive liposomes, the negative liposomes were preferredfor 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 ofsurface charge of the liposomes. Renal concentrations of gentamicin were lower (3 to 5folds) with liposomes, and uptake was not charge dependent.In conclusion, a simple method for preparation of liposomes was adopted. The distributionstudies suggested that positively charged liposomes had highest affinity for the brain and thenegative liposomes for the liver. Also, liposomes irrespective of charge exhibited reducedrenal concentration of gentamicin.

[发布机构] University of the Free State