Abstract

A new drug and dye delivery system is proposed to allow repeated release of substances in the ocular vasculature under external control. The substances are encapsulated in heat-sensitive liposomes¹ which are lysed by locally applying a heat pulse produced by an argon laser. The feasibility of lysing heat-sensitive liposomes by laser irradiation was first tested in vitro by encapsulating carboxyfluorescein and monitoring its release. The liposomes’ suspension was dialyzed, to remove the dye that was not encapsulated, and diluted 400 times in calf serum to mimic the dilution factor expected in humans following a slow intravenous injection of about 12cc of liposomes. The preparation was placed in a cuvette and incubated in a bath at 37°C or 38.5°C. A commercial ophthalmic argon laser was used to deliver pulses of blue light at 488nm. The cuvette was placed away from the focal plane to obtain a beam spot 2 mm in diameter which covered the whole sample. The amount of carboxyfluorescein released was assessed by measuring its fluorescence with a commercial fluorophotometer. The release yield was calculated as the ratio between the fluorescence of the irradiated sample and that of a controlled sample heated at he liposome transition temperature of 41°C. The results indicated that up to 85% of the original liposome content could be released by the exposure to the laser. We verified that the system behaved as anticipated by varying the incubating temperature. As the incubation temperature approached the transition temperature of 41°C, less energy was required to lyse the liposomes. Moreover, the release yield changed with energy in a manner similar to that of liposomes lysed by slowly heating the medium,¹ indicating that the mechanism of release was not influenced by the fact that short pulses are used (50 to 500 msec). Of special importance was the observation that the non-irradiated liposomes exhibited minimal fluorescence due to concentration quenching while an intense fluorescence was present where carboxyfluorescein was released and diluted in the plasma following the lysis of the liposomes.

© 1988 Optical Society of America