P2B-7 Dosage Prediction via Shell Thickness Estimation of Drug Carrier with Microbubbles

For drug delivery applications, dosage prediction before release and estimation after release are required functions. The difference of harmonic responses generated from multi-lamellar vesicles with different numbers of layers can be used to estimate the shell thickness related to numbers of layers and predict the dosage of vesicles. However, there is no appropriate mathematical model and experimental protocol to determine the shell thickness of multi-lamellar vesicles. In this study, we use the Trilling model with parameter of phospholipids bilayers to simulate the frequency responses and establish an experimental protocol to evaluate the shell thickness of liposomes. From simulation, it is shown that thinner layers will increase the second harmonic response. We make liposomes consisting of gas for experimental test, with mean diameter being 1 micron meter and shell thickness being 1 to 5 layers. The shell thickness of liposome is controlled by sonicator which can diminish the numbers of layers. To test the liposomes with different shell thickness, pulse trains (PRF = 1 KHz, B.W. = 5%) are transmitted with center frequencies at 2 MHz and 1.75 MHz, then backscattered signals are received and digitized for processing. For the 2 MHz experiment, referred to the echo of liposomes with 3 to 5 layers, the second harmonic response generated by liposomes with 1 to 2 layers is about 5 dB higher. For the 1.75 MHz experiment, the increase is about 6 dB. The trends of signal dependence on the thickness and center frequency agree with the simulation studies. The simulations are done for liposomes with 4-layers shell and 1-layers shell; the difference of their second harmonic intensities with center frequency at 2 MHz and 1.75 MHz should be about 12 dB. Reasons for this discrepancy are to be studied in the nature. Possible reasons include: distributed shell thickness in experiments and etc. Therefore, in accordance with the theoretical and experimental result, we would be able to- estimate the shell thickness of the liposomes. A potential application of this method is to predict the dosage of liposomes (especially lipid soluble medicines) further