Preparation, properties and the effects of free and liposomal tobramycin on siderophore production by Pseudomonas aeruginosa.
The in-vitro activities of encapsulated and free tobramycin were evaluated against Pseudomonas aeruginosa grown in iron-depleted chemically-defined culture medium (CDM-Fe). The liposomal formulations used for the efficacy studies of encapsulated tobramycin were based on the optimal loading and release patterns. The dehydration-rehydration (DRV) technique was used to prepare fluid phosphatidylcholine (PC) and solid, distearylphosphatidylcholine (DSPC), neutral, negatively charged phosphatidic acid (PA) and positively charged stearylamine (SA) liposomes containing tobramycin. The total charged phospholipid in each preparation was no more than 5% of the total phospholipid content. The effects of free and liposome-encapsulated tobramycin on siderophore production by P. aeruginosa were examined and involved using MIC and sub-MIC quantities of tobramycin: 0.25, 0.125, 0.0625 and 0.025 mg/L, corresponding to 1, 0.5, 0.25 and 0.1 times MIC, respectively, were used. Compared to free tobramycin, siderophore production was more effectively retarded in the presence of sub-MIC quantities of liposomal tobramycin, particularly at 0.5 MIC. Siderophore production was particularly reduced in the presence of positively charged PC liposomes.
Pharmaceutical Sciences Institute, Aston University, Aston Triangle, Birmingham, UK.
E A
EA
Poyner
H O
HO
Alpar
M R
MR
Brown
D002626:Chemistry, Pharmaceutical; D004337:Drug Carriers; D007700:Kinetics; D008081:Liposomes; D008826:Microbial Sensitivity Tests; D010713:Phosphatidylcholines / Q000737:chemistry; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000378:metabolism*; D017262:Siderophores / Q000096:biosynthesis*; D013499:Surface Properties; D014031:Tobramycin / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology*
D004337:Drug Carriers; D008081:Liposomes; D010713:Phosphatidylcholines; D017262:Siderophores; C010942:1,2-distearoyllecithin; D014031:Tobramycin