direct injection
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AbstractDirect injection of therapies into tumors has emerged as an administration route capable of achieving high local drug exposure and strong anti-tumor response. A diverse array of immune agonists ranging in size and target are under development as local immunotherapies. However, due to the relatively recent adoption of intratumoral administration, the pharmacokinetics of locally-injected biologics remains poorly defined, limiting rational design of tumor-localized immunotherapies. Here we define a pharmacokinetic framework for biologics injected intratumorally that can predict tumor exposure and effectiveness. We find empirically and computationally that extending the tumor exposure of locally-injected interleukin-2 by increasing molecular size and/or improving matrix-targeting affinity improves therapeutic efficacy in mice. By tracking the distribution of intratumorally-injected proteins using positron emission tomography, we observe size-dependent enhancement in tumor exposure occurs by slowing the rate of diffusive escape from the tumor and by increasing partitioning to an apparent viscous region of the tumor. In elucidating how molecular weight and matrix binding interplay to determine tumor exposure, our model can aid in the design of intratumoral therapies to exert maximal therapeutic effect.

The regeneration of nerve tissue after spinal cord injury is a complex and poorly understood process. Medication and surgery are not very effective treatments for patients with spinal cord injuries. Gene therapy is a popular approach for the treatment of such patients. The delivery of therapeutic genes is carried out in a variety of ways, such as direct injection of therapeutic vectors at the site of injury, retrograde delivery of vectors, and ex vivo therapy using various cells. Recombinant adenoviruses are often used as vectors for gene transfer. This review discusses the advantages, limitations and prospects of adenovectors in spinal cord injury therapy.

Mineral oil has been used as an insulating fluid in the power industry. However, surplus waste oil poses serious environmental threats because of disposal concerns. Waste to biofuel is an excellent way to deal with waste material from various sources. In this study, the trans-esterification method was utilised to convert the waste-insulating mineral oil into a quality bio-fuel. Waste-insulating transformer oil was converted to biodiesel, and it was tested according to ASTM standards. Four different blends of waste-insulating biodiesel with diesel in 25 per cent (WIOBD25), 50 per cent (WIOBD50), 75 per cent (WIOBD75), and 100 per cent fractions (WIOBD100), were used for performance testing in a direct injection compression ignition (DICI) engine. The combustion parameters such as BSFC, EGT, and BTE were evaluated with varying crank angles and constant engine speed. The waste-insulating biodiesel performance results are then compared with diesel fuel. BSFC increased as the biofuel mixture in diesel was raised, and the brake thermal efficiency (BTE) was significantly reduced compared to diesel for all WIOBD diesel mixtures. Due to the combustion process, a high pressure and heat release rate (HRR) were noticed inside the cylinder with the waste-insulating oil-derived biodiesel samples. WIOBD biodiesel blends produced lower levels of hydrocarbon, carbon monoxide, and smoke emissions than diesel fuel, but greater levels of nitrogen oxides (NOx) were produced than diesel fuel. In addition to lower emissions combined with improved engine performance, the WIOBD25 fuel blend has been found to be experimentally optimal for practical application. As a result, the test findings indicated that WIOBD biodiesel might be used as a substitute for conventional diesel fuel.