Advancing the frontiers of silk fibroin protein-based materials for futuristic electronics and clinical wound-healing (Invited review).

The present review will introduce the basic concepts of silk-based electronics/optoelectronics including the latest technological advances on the use of silk fibroin in combination with other functional components, with an emphasis on improving the performance of next-generation silk-based materials. It also highlights the patterning of silk fibroin to produce micro/nano-scale features, as well as the functionalization of silk fibroin to impart antimicrobial (i.e. antibacterial) properties. Silk-based bioelectronics have great potential for advanced or futuristic bio-applications including e-skins, e-bandages, biosensors, wearable displays, implantable devices, artificial muscles, etc. Notably, silk-based organic field-effect transistors have highly promising applications in e-skins and biosensors; silk-based electrodes/antennas are used for in vivo bioanalysis or sensing purpose (e.g., measurement of neurotransmitter such as dopamine) in addition to their use as food sensors; silk-based diodes can be applied as light sources for wound healing or tissue engineering, e.g., in cutaneous wound closure or induction of photothrombosis of corneal neovascularization; silk-based actuators have promising applications as artificial muscles; whereas silk-based memristors have exciting applications as logic or synaptic network for realizing e-skins or bionic brains.

Depot delivery of dexamethasone and cediranib for the treatment of brain tumor associated edema in an intracranial rat glioma model.

Treatments of brain tumor associated edema with systemically delivered dexamethasone, the standard of care, and cediranib, a novel anti-edema agent, are associated with systemic toxicities in brain tumor patients. A tunable, reservoir-based drug delivery device was developed to investigate the effects of delivering dexamethasone and cediranib locally in the brain in an intracranial 9L gliosarcoma rat model. Reproducible, sustained releases of both dexamethasone and solid dispersion of cediranib in polyvinylpyrrolidone (AZD/PVP) from these devices were achieved. The water-soluble AZD/PVP, which exhibited similar bioactivity as cediranib, was developed to enhance the release of cediranib from the device. Local and systemic administration of both dexamethasone and cediranib was equally efficacious in alleviating edema but had no effect on tumor growth. Edema reduction led to modest but significant improvement in survival. Local delivery of dexamethasone prevented dexamethasone-induced weight loss, an adverse effect seen in animals treated with systemic dexamethasone. Local deliveries of dexamethasone and cediranib via these devices used only 2.36% and 0.21% of the systemic doses respectively, but achieved similar efficacy as systemic drug deliveries without the side effects associated with systemic administration. Other therapeutic agents targeting brain tumor can be delivered locally in the brain to provide similar improved treatment outcomes.

Single compartment drug delivery.

Drug design is built on the concept that key molecular targets of disease are isolated in the diseased tissue. Systemic drug administration would be sufficient for targeting in such a case. It is, however, common for enzymes or receptors that are integral to disease to be structurally similar or identical to those that play important biological roles in normal tissues of the body. Additionally, systemic administration may not lead to local drug concentrations high enough to yield disease modification because of rapid systemic metabolism or lack of sufficient partitioning into the diseased tissue compartment. This review focuses on drug delivery methods that physically target drugs to individual compartments of the body. Compartments such as the bladder, peritoneum, brain, eye and skin are often sites of disease and can sometimes be viewed as "privileged," since they intrinsically hinder partitioning of systemically administered agents. These compartments have become the focus of a wide array of procedures and devices for direct administration of drugs. We discuss the rationale behind single compartment drug delivery for each of these compartments, and give an overview of examples at different development stages, from the lab bench to phase III clinical trials to clinical practice. We approach single compartment drug delivery from both a translational and a technological perspective.