Abstract
Context: Triggering drug release from delivery vehicles with ultrasound has potential applications in targeted drug delivery. It was hypothesized that the addition of bile salts would increase the sensitivity of liposomes to ultrasound through creation of defects.
Objective: The aim of this study was to investigate whether incorporating bile salts into liposomes would lead to differential effects on their response to low and high frequency ultrasound.
Materials and methods: Cholate, chenodeoxycholate, ursodeoxycholate, glycocholate and taurocholate were the selected bile salts. Response to ultrasound was characterized by measuring the release of carboxyfluorescein (CF).
Results: At 30 kHz ultrasound, taurocholate containing liposomes were most responsive and released 70% (±2) CF after 30 seconds of sonication. Compared to this, liposomes that did not contain bile salts released just 7% (±2). At 1.1 MHz ultrasound, all liposome formulations were unresponsive. To increase the response of liposomes at 1.1 MHz ultrasound, a combination of membrane destabilizers were added to DSPC liposomes. DOPE, a hexagonal phase lipid was used in combination with taurocholate. Surprisingly, liposomes containing DOPE and taurocholate were more resistant to 1.1 MHz ultrasound than ones containing only DOPE.
Discussion: This suggests that the sensitivity of liposomes towards ultrasound may not simply be defined by a single membrane component but instead depends on the interaction between constituting lipid components. Furthermore, strategies other than membrane destabilization may be required to sensitize liposomes towards high frequency ultrasound.
Conclusion: Bile salts may be used to increase or decrease the sensitivity of liposomes to low frequency ultrasound.
Acknowledgements
Authors thank Dr J Paul Fawcett for the many helpful suggestions.
Declaration of interest
The authors are not aware of any professional, or personal bias, inclination, obligation or loyalty which may conflict with the impartiality of this document. The authors would like to thank NZPERF for providing funding for materials and also Lipoid for gifting the Soy Lecithin.