Noninvasive Ultrasound Mediated Transdermal Transport of Insulin Across Ex Vivo Human Skin

Author(s):  
Nadine Barrie Smith ◽  
Seungjun Lee ◽  
K. Kirk Shung

The purpose of this research was to improve low frequency (20 kHz) ultrasound methods for enhancing the transport of insulin across ex vivo human skin. The feasibility of using ultrasound produced by small, lightweight novel transducers was explored for enhancing the transport of insulin across skin. Previous investigators have used ultrasound devices such as large, heavy sonicators or commercially obtained transducers for this type of research. These experiments used two low-profile novel ultrasound transducer arrays, the stack and standard array, for improved transport of insulin. The stack array was driven with a spatial peak temporal peak intensity (Isptp) of 15.5 ± 2.0 mW/cm2 while the standard array had an Isptp of 173.7 ± 9.1 mW/cm2. Spectrophotometeric absorption techniques were used for determining insulin transport across ex vivo human skin. Compared to passive transmission (6.3 ± 14.0 U/hr), the standard array facilitated a 6-fold increase in the noninvasive transdermal transport of Humulin® insulin (39.6 ± 11.7 U/hr). These promising results indicate that low frequency ultrasound can be used in a practical device for enhanced transport across the stratum corneum.

2020 ◽  
Vol 117 (23) ◽  
pp. 12674-12685
Author(s):  
Tali Ilovitsh ◽  
Yi Feng ◽  
Josquin Foiret ◽  
Azadeh Kheirolomoom ◽  
Hua Zhang ◽  
...  

Robust cytotoxic T cell infiltration has proven to be difficult to achieve in solid tumors. We set out to develop a flexible protocol to efficiently transfect tumor and stromal cells to produce immune-activating cytokines, and thus enhance T cell infiltration while debulking tumor mass. By combining ultrasound with tumor-targeted microbubbles, membrane pores are created and facilitate a controllable and local transfection. Here, we applied a substantially lower transmission frequency (250 kHz) than applied previously. The resulting microbubble oscillation was significantly enhanced, reaching an effective expansion ratio of 35 for a peak negative pressure of 500 kPa in vitro. Combining low-frequency ultrasound with tumor-targeted microbubbles and a DNA plasmid construct, 20% of tumor cells remained viable, and ∼20% of these remaining cells were transfected with a reporter gene both in vitro and in vivo. The majority of cells transfected in vivo were mucin 1+/CD45−tumor cells. Tumor and stromal cells were then transfected with plasmid DNA encoding IFN-β, producing 150 pg/106cells in vitro, a 150-fold increase compared to no-ultrasound or no-plasmid controls and a 50-fold increase compared to treatment with targeted microbubbles and ultrasound (without IFN-β). This enhancement in secretion exceeds previously reported fourfold to fivefold increases with other in vitro treatments. Combined with intraperitoneal administration of checkpoint inhibition, a single application of IFN-β plasmid transfection reduced tumor growth in vivo and recruited efficacious immune cells at both the local and distant tumor sites.


2003 ◽  
Vol 112 (1-2) ◽  
pp. 99-104 ◽  
Author(s):  
Yoram Neuman ◽  
Vladimir Rukshin ◽  
Vivian Tsang ◽  
Shaul Atar ◽  
Takashi Miyamoto ◽  
...  

2020 ◽  
pp. 13-23
Author(s):  
Natalya Kornova ◽  
A. Krylov

The article presents results of a study on the effectiveness of using lowfrequency ultrasound and photochromotherapy in the complex treatment of patients with chronic bacterial and viral rhinosinusitis. The study involved 69 people aged 18 to 55 years: 39 (56.83 %) women and 30 (45.11 %) men with chronic rhinosinusitis during the period of clinical exacerbation and concomitant chronic tonsillitis without exacerbation. All patients included in the study underwent X-ray examination or computed tomography and magnetic resonance imaging of the paranasal sinuses. 100 % of the patients were examined for the presence of antibodies to Human gammaherpesvirus 4 (ELISA), had study of blood serum for IgM and IgG and test to determine the avidity of Ig G antibodies to γ-herpesviruses. The obtained data indicate the effectiveness of including low-frequency ultrasound and photochromotherapy in the complex treatment of patients with chronic rhinosinusitis and concomitant chronic tonsillitis of bacterial and viral nature without exacerbation.


Author(s):  
Mohd Razealy Anuar ◽  
Mohamed Hussein Abdurahman ◽  
Nor Irwin Basir ◽  
Ahmad Zuhairi Abdullah

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