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4. Acoustic metamaterials-driven transdermal drug delivery for rapid and on-demand management of acute disease.

Author

Xu, Junhua, Cai, Hongwei, Wu, Zhuhao, Li, Xiang, Tian, Chunhui, Ao, Zheng, Niu, Vivian C, Xiao, Xiao, Jiang, Lei, Khodoun, Marat, Rothenberg, Marc, Mackie, Ken, Chen, Jun, Lee, Luke P, and Guo, Feng

Subjects
Skin, Animals, Mice, Acute Disease, Drug Delivery Systems, Administration, Cutaneous, Acoustics, Female, Rare Diseases, Orphan Drug, Biotechnology, 5.1 Pharmaceuticals, Development of treatments and therapeutic interventions, Good Health and Well Being
Abstract

Transdermal drug delivery provides convenient and pain-free self-administration for personalized therapy. However, challenges remain in treating acute diseases mainly due to their inability to timely administrate therapeutics and precisely regulate pharmacokinetics within a short time window. Here we report the development of active acoustic metamaterials-driven transdermal drug delivery for rapid and on-demand acute disease management. Through the integration of active acoustic metamaterials, a compact therapeutic patch is integrated for penetration of skin stratum corneum and active percutaneous transport of therapeutics with precise control of dose and rate over time. Moreover, the patch device quantitatively regulates the dosage and release kinetics of therapeutics and achieves better delivery performance in vivo than through subcutaneous injection. As a proof-of-concept application, we show our method can reverse life-threatening acute allergic reactions in a female mouse model of anaphylaxis via a multi-burst delivery of epinephrine, showing better efficacy than a fixed dosage injection of epinephrine, which is the current gold standard 'self-injectable epinephrine' strategy. This innovative method may provide a promising means to manage acute disease for personalized medicine.

Published
2023

48. Relaxin inhibits 177Lu-EDTMP associated cell death in osteosarcoma cells through notch-1 pathway

Author

Xu Junhua, Wan Song, Chen Wei, Zhang Yi, and Ji Zhenzhong

Subjects
osteosarcoma, relaxin-2, cell death, apoptosis, notch-1 pathway, Pharmaceutical industry, HD9665-9675
Abstract

177Lu-EDTMP (Ethylenediamine tetramethylene phosphonic acid) is the most used radioactive agent for pain palliation in bone cancer patients. The present study aims to study the impact of relaxin-2 on the 177Lu-EDTMP associated cell toxicity and death in osteosarcoma cells. MG63 and Saos-2 cells were cultured with 177Lu-EDTMP (37 MBq) for 24 h with and without pretreatment of recombinant relaxin 2 (RLXH2) for 12 and 24 h. 177Lu-EDTMP associated cellular deterioration and death was determined by LDH, MTT, and trypan blue dye assays. ELISA-based kit was used to determine apoptotic DNA fragmentation. Western blotting was used to determine expression levels of apoptotic-related signalling pathway proteins like bcl2, poly(ADP-ribose) polymerase (PARP), and MAPK (mitogen-activated protein kinase). Our results found that RLXH2 counters 177Lu-EDTMP associated cellular toxicity. Similarly, RLXH2 was able to counter 177Lu-EDTMP induced cell death in a concentration and time--dependent manner. Furthermore, it was found that RLXH2 treatment prevents apoptosis in 177Lu-EDTMP challenged cells through activation of the notch-1 pathway in a concentration- and time-dependent manner. We reported that RLXH2 significantly declined cellular toxicity and apoptosis associated with 177Lu-EDTMP in MG63 and Saos-2 cells through the notch-1 pathway.

Published
2022
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