박준홍 Lee, Seunghyun Jeon Ho yoon Kim, Jung Hoon Kim, Da Jung Im, Maesoon Lee, Byung Chul 2024-01-12T06:35:14Z 2024-01-12T06:35:14Z 2023-06-22 2023-07 0378-5173 https://pubs.kist.re.kr/handle/201004/79884 Target-specific drug release is indispensable to improve chemotherapeutic efficacy as it enhances drug uptake and penetration into tumors. Sono-responsive drug-loaded nano-/micro-particles are a promising solution for achieving target specificity by exposing them to ultrasound near tumors. However, the complicated synthetic processes and limited ultrasound (US) exposure conditions, such as limited control of ultrasound focal depth and acoustic power, prevent the practical application of this approach in clinical practice. Here, we propose a convex acoustic lens-attached US (CALUS) as a simple, economic, and efficient alternative of focused US for drug delivery system (DDS) application. The CALUS was characterized both numerically and experimentally using a hydrophone. In vitro, microbubbles (MBs) inside microfluidic channels were destroyed using the CALUS with various acoustic parameters (acoustic pressure [P], pulse repetition frequency [PRF], and duty cycle) and flow velocity. In vivo, tumor inhibition was evaluated using melanoma-bearing mice by characterizing tumor growth rate, animal weight, and intratumoral drug concentration with/without CALUS DDS. US beams were measured to be efficiently converged by CALUS, which was consistent with our simulation results. The acoustic parameters were optimized through the CALUS-induced MB destruction test (P = 2.34 MPa, PRF = 100 kHz, and duty cycle = 9%); this optimal parameter combination successfully induced MB destruction inside the microfluidic channel with an average flow velocity of up to 9.6 cm/s. The CALUS also enhanced the therapeutic effects of an antitumor drug (doxorubicin) in vivo in a murine melanoma model. The combination of the doxorubicin and the CALUS inhibited tumor growth by ∼ 55% more than doxorubicin alone, clearly indicating synergistic antitumor efficacy. Our tumor growth inhibition performance was better than other methods based on drug carriers, even without a time-consuming and complicated chemical synthesis process. This result suggests that our novel, simple, economic, and efficient target-specific DDS may offer a transition from preclinical research to clinical trials and a potential treatment approach for patient-centered healthcare. English Elsevier BV A novel convex acoustic lens-attached ultrasound drug delivery system and its testing in a murine melanoma subcutaneous model Article 10.1016/j.ijpharm.2023.123118 1 International Journal of Pharmaceutics, v.642 International Journal of Pharmaceutics 642 Y scie scopus 001032977300001 Pharmacology & Pharmacy Pharmacology & Pharmacy Article BLOOD-FLOW-VELOCITY FOCUSED ULTRASOUND MEDIATED DELIVERY CANCER BRAIN PHASE PERMEABILITY EFFICACY DESIGN TUMORS Acoustic lens Ultrasound-mediated microbubble destruction Drug delivery Doxorubicin Melanoma tumor The authors would like to especially thank Yong Sub Shin (SNUH) for animal modeling and imaging scans