On the microstructurally driven heterogeneous response of brain white matter to drug infusion pressure.

Delivering therapeutic agents into the brain via convection-enhanced delivery (CED), a mechanically controlled infusion method, provides an efficient approach to bypass the blood-brain barrier and deliver drugs directly to the targeted focus in the brain. Mathematical methods based on Darcy's law have been widely adopted to predict drug distribution in the brain to improve the accuracy and reduce the side effects of this technique. However, most of the current studies assume that the hydraulic permeability and porosity of brain tissue are homogeneous and constant during the infusion process, which is less accurate due to the deformability of the axonal structures and the extracellular matrix in brain white matter.

Insights into Infusion-Based Targeted Drug Delivery in the Brain: Perspectives, Challenges and Opportunities.

Targeted drug delivery in the brain is instrumental in the treatment of lethal brain diseases, such as glioblastoma multiforme, the most aggressive primary central nervous system tumour in adults. Infusion-based drug delivery techniques, which directly administer to the tissue for local treatment, as in convection-enhanced delivery (CED), provide an important opportunity; however, poor understanding of the pressure-driven drug transport mechanisms in the brain has hindered its ultimate success in clinical applications. In this review, we focus on the biomechanical and biochemical aspects of infusion-based targeted drug delivery in the brain and look into the underlying molecular level mechanisms.

Microscale characterisation of the time-dependent mechanical behaviour of brain white matter.

Brain mechanics is a topic of deep interest because of the significant role of mechanical cues in both brain function and form. Specifically, capturing the heterogeneous and anisotropic behaviour of cerebral white matter (WM) is extremely challenging and yet the data on WM at a spatial resolution relevant to tissue components are sparse. To investigate the time-dependent mechanical behaviour of WM, and its dependence on local microstructural features when subjected to small deformations, we conducted atomic force microscopy (AFM) stress relaxation experiments on corpus callosum (CC), corona radiata (CR) and fornix (FO) of fresh ovine brain.

Humanin: A mitochondrial-derived peptide in the treatment of apoptosis-related diseases.

Humanin (HN) is a small mitochondrial-derived cytoprotective polypeptide encoded by mtDNA. HN exhibits protective effects in several cell types, including leukocytes, germ cells, neurons, tissues against cellular stress conditions and apoptosis through regulating various signaling mechanisms, such as JAK/STAT pathway and interaction of BCL-2 family of protein. HN is an essential cytoprotective peptide in the human body that regulates mitochondrial functions under stress conditions.

Infusion Mechanisms in Brain White Matter and Their Dependence on Microstructure: An Experimental Study of Hydraulic Permeability.

Hydraulic permeability is a topic of deep interest in biological materials because of its important role in a range of drug delivery-based therapies. The strong dependence of permeability on the geometry and topology of pore structure and the lack of detailed knowledge of these parameters in the case of brain tissue makes the study more challenging. Although theoretical models have been developed for hydraulic permeability, there is limited consensus on the validity of existing experimental evidence to complement these models.

Solvent-controlled reversible switching between adsorbed self-assembled nanoribbons and nanotubes.

We have demonstrated that solutions of 3,5-bis-(5-hexylcarbamoylpentyloxy)-benzoic acid decyl ester (BHPB-10) can form metastable nanostructures on solid substrates and in the bulk. BHPB-10 is an achiral molecule involving several distinct, strongly interacting groups (SIGs), one aromatic-ester ring and two amide groups per molecule. Specific solvents affect the interactions between particular SIGs, thus promoting various nano-structures: lamellae, nanoribbons, helical ribbons, or nanotubes.