Ultrasonic drug release: Impact on liposomal doxorubicin in collagen gels

Ultrasound enhances the release of drugs from liposomes, and in solution this is shown to be caused by cavitation. However, the mechanism in tissue is unclear, and there is a need to bridge the gap between results obtained in solution and in tissue. Thus, we studied the release of liposomal doxorubicin in 5% w/v type I rattail collagen gels when subjected to 300 MHz ultrasound. Confocal laser scanning imaging was used to characterize the gels before and after the treatment, and for determining the release of doxorubicin. The results indicate that drug release in collagen gels is similar to that in liquid, due to mechanical effects (cavitation) rather than thermal ones. Release was shown to be highly dependent on the presence of gas bubbles by degassing and adding controlled amounts of gas contrast bubbles, and the drug release correlated with the presence of OH radicals. Compared to experiments in solution, the threshold at which such effects happen is similar, at a negative pressure of 0.9 MPa, but the maximum release is halved for identical treatment.