Targeted delivery of therapeutic agents to the mouse brain using a stereotactic-guided focused ultrasound device

Existing protocols of focused ultrasound (FUS) combined with microbubble-mediated blood-brain barrier (BBB) opening (FUS-BBBO) in preclinical research require expensive ultrasound equipment and complex operating procedures. We developed a low-cost, easy-to-use, and precise FUS device for small animal models in preclinical research. Here, we provide a detailed protocol for building the FUS transducer, attaching the transducer to a stereotactic frame for precise brain targeting, applying the integrated FUS device to perform FUS-BBBO in mice, and evaluating the FUS-BBBO outcome. For complete details on the use and execution of this protocol, please refer to Hu et al. (2022)

Focused ultrasound-mediated delivery of anti-programmed cell death-ligand 1 antibody to the brain of a porcine model

Immune checkpoint inhibitor (ICI) therapy has revolutionized cancer treatment by leveraging the body\u27s immune system to combat cancer cells. However, its effectiveness in brain cancer is hindered by the blood-brain barrier (BBB), impeding the delivery of ICIs to brain tumor cells. This study aimed to assess the safety and feasibility of using focused ultrasound combined with microbubble-mediated BBB opening (FUS-BBBO) to facilitate trans-BBB delivery of an ICI, anti-programmed cell death-ligand 1 antibody (aPD-L1) to the brain of a large animal model. In a porcine model, FUS sonication of targeted brain regions was performed after intravenous microbubble injection, which was followed by intravenous administration of aPD-L1 labeled with a near-infrared fluorescent dye. The permeability of the BBB was evaluated using contrast-enhanced MRI in vivo, while fluorescence imaging and histological analysis were conducted on ex vivo pig brains. Results showed a significant 4.8-fold increase in MRI contrast-enhancement volume in FUS-targeted regions compared to nontargeted regions. FUS sonication enhanced aPD-L1 delivery by an average of 2.1-fold, according to fluorescence imaging. In vivo MRI and ex vivo staining revealed that the procedure did not cause significant acute tissue damage. These findings demonstrate that FUS-BBBO offers a noninvasive, localized, and safe delivery approach for ICI delivery in a large animal model, showcasing its potential for clinical translation

Implementation of a Health Policy Advisory Committee as a Knowledge Translation Platform: The Nigeria Experience

Background: In recent times, there has been a growing demand internationally for health policies to be based on reliable research evidence. Consequently, there is a need to strengthen institutions and mechanisms that can promote interactions among researchers, policy-makers and other stakeholders who can influence the uptake of research findings. The Health Policy Advisory Committee (HPAC) is one of such mechanisms that can serve as an excellent forum for the interaction of policy-makers and researchers. Therefore, the need to have a long term mechanism that allows for periodic interactions between researchers and policy-makers within the existing government system necessitated our implementation of a newly established HPAC in Ebonyi State Nigeria, as a Knowledge Translation (KT) platform. The key study objective was to enhance the capacity of the HPAC and equip its members with the skills/competence required for the committee to effectively promote evidence informed policy-making and function as a KT platform. Methods:A series of capacity building programmes and KT activities were undertaken including: i) Capacity building of the HPAC using Evidence-to-Policy Network (EVIPNet) SUPPORT tools; ii) Capacity enhancement mentorship programme of the HPAC through a three-month executive training programme on health policy/health systems and KT in Ebonyi State University Abakaliki; iii) Production of a policy brief on strategies to improve the performance of the Government’s Free Maternal and Child Health Care Programme in Ebonyi State Nigeria; and iv) Hosting of a multi-stakeholders policy dialogue based on the produced policy brief on the Government’s Free Maternal and Child Health Care Programme. Results:The study findings indicated a noteworthy improvement in knowledge of evidence-to-policy link among the HPAC members; the elimination of mutual mistrust between policy-makers and researchers; and an increase in the awareness of importance of HPAC in the Ministry of Health (MoH). Conclusion: Findings from this study suggest that a HPAC can function as a KT platform and can introduce a new dimension towards facilitating evidence-to-policy link into the operation of the MoH, and can serve as an excellent platform to bridge the gap between research and policy