Enhanced activity of liposomes-encapsulated antibiotics against clinical isolates of Pseudomonas aeruginosa has been documented with liposomes of low encapsulation efficiency. We sought to construct liposomes with high yield entrapment of aminoglycoside and macrolide antibiotics as well as favorable stability in storage and physiological conditions. Liposome-entrapped aminoglycosides (amikacin, gentamicin, tobramycin) and a macrolide (erythromycin) were prepared by a modified dehydration-rehydration vesicles (DRVs) method, and their particle size and entrapment efficiency were determined. We studied in vitro stability of these vesicles over a 48 h period at 4 and 37 degrees C in phosphate-buffered saline (PBS) and in plasma at 37 degrees C. The mean particle size of DRVs loaded with antibiotics varied from 163.37+/-38.44 to 259.83+/-11.80 nm with no significant difference in regard with the type of the antibiotics encapsulated. Encapsulation efficiency of DRVs loaded with amikacin, gentamicin, tobramycin, and erythromycin were 29.27+/-1.17, 33+/-0.76, 22.33+/-1.48 and 32.06+/-0.82% of initial amount of the drug, respectively. These vesicles were stable regardless of the experimental temperature. Indeed, the liposomes retained more than 75% of the initially encapsulated drugs for the study period of 48 h. DRVs incubated in plasma however, released more antibiotics than those incubated in PBS. In conclusion, using this modified DRV method, we obtained small sized vesicles with high yield entrapment for aminoglycoside and macrolide antibiotics. The technique may be utilized to overcome the low encapsulation efficiency associated with aminoglycoside and macrolide antibiotics.