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Effective blood-brain tumor barrier penetration and uniform solid tumor distribution can significantly enhance therapeutic delivery to brain tumors. Hydroxyl-functionalized, generation-4 poly(amidoamine) (PAMAM) dendrimers, with their small size, near-neutral surface charge, and the ability to selectively localize in cells associated with neuroinflammation may offer new opportunities to address these challenges. In this study we characterized the intracranial tumor biodistribution of systemically delivered PAMAM dendrimers in an intracranial rodent gliosarcoma model using fluorescence-based quantification methods and high resolution confocal microscopy. We observed selective and homogeneous distribution of dendrimer throughout the solid tumor (~6mm) and peritumoral area within fifteen minutes after systemic administration, with subsequent accumulation and retention in tumor associated microglia/macrophages (TAMs). Neuroinflammation and TAMs have important growth promoting and pro-invasive effects in brain tumors. The rapid clearance of systemically administered dendrimers from major organs promises minimal off-target adverse effects of conjugated drugs. Therefore, selective delivery of immunomodulatory molecules to TAM, using hydroxyl PAMAM dendrimers, may hold promise for therapy of glioblastoma.

Drug carrier particles composed of poly(ethylene glycol)-co-poly(sebacic acid) (PEG-PSA) have been shown capable of efficient aerosolization into model lungs and the ability to rapidly penetrate human mucus. Here, we develop PEG-PSA particles (Etop/PEG-PSA) that encapsulate up to 40% etoposide by weight in a one step process, release it continuously for 6 days in vitro, and maintain its cytotoxic activity against a human lung tumor cell line in vitro. We further show that Etop/PEG-PSA injected intratumorally effectively suppress human lung tumor growth in a xenograft mouse model, with 100% survival after 31 days. In contrast, 0% survival was observed by day 24 in animals that received free etoposide (either intratumoral or intraperitoneal administration) or placebo particles intratumorally. These findings support PEG-PSA as a drug delivery platform for improved local therapy of cancer. © 2009 Elsevier Ltd. All rights reserved.

There have been some developments in understanding the outburst mechanism and improving the control of in seam drilling. Experience with techniques for draining from the surface has shown promise. There is a need for operators to provide facilities for more research so that the outburst phenomenon can bet better understood.

In-seam drilling has two main purposes: gas drainage and exploration. Each hole can yield information on the geological structure of the ground drilled, but in the drilling of some gas drainage holes, valuable geological data is lost. Drilling technology has changed in some ways over the last ten years, but still has some way to go. There is room for more improvements to reduce the costs, to reduce the risks and to increase the information gathered.

This paper summarises some of the development of the understanding and management of outbursts in Australia, reviews the current situation and provides some thoughts on necessary research and development. It cannot be and is not comprehensive. Outbursts are better understood, prevented or controlled than they were 20 years ago. This is partly a result of the considerable amount of research into and documentation of outbursts and gas by a relatively small group of outburst pioneers supported by the coal industry. The result has been fewer outbursts in general, and the safe mining through a few potential outburst zones without risk to personnel. It is not time to rest on our laurels. Outburst and gas investigation needs to be continued, supported by industry, so that all outburst related phenomena and advances in gas management can be documented and communicated to all players.

In-seam drilling is conducted mainly to drain coal of gas and/or water prior to development or extraction. The requirements of inseam drilling for gas drainage have mainly surpassed the technical limits of rotary drilling and are mainly being addressed by guided down hole motor drilling, albeit at a higher cost. There is an increasing application of in-seam drilling to detect geological structures or other hazards or their absence in advance of mining to reduce the risks of underground mining. Close collaboration between miners, drillers, geologists, researchers and suppliers over the last four years has seen many advances made to improve the accuracy and reliability of inseam drilling. With such developments will come closer control over the ventilation and safety of future mining under deep gassy conditions, but not without costs. The paper summarises the current applications of inseam drilling, recent technological advances and the next generation survey and geophysical sensing tools which are currently being developed