how rapidly bloodstream and pulmonary lymphatic drainage can eliminate products of nanoparticles degradation general safety concerns add to these specific issues that are pertinent to pulmonary targeting strictly speaking, the actual biocompatibility of materials for carriers remains unknown, until it is carefully tested in adequate clinical settings using carriers of adequate size for example, nanocarriers based on polylactic glycolic acid polymer, accepted for human use for macroimplants, may degrade into lactic zoloft sri acid and glycolic acid within the target cells, potentially exceeding its metabolic potential potentially harmful effects of activation systemic defense systems ie complement, cytokines, zoloft sri overload of clearance systems eg liver, kidneys and immune reactions, represent general concerns of advanced delivery systems however, despite these concerns, the most exciting prospect of nanocarriers are the near limitless possibilities for treatment strategies nanocarriers may be designed to contain multiple drugs, allowing for complex dosing regimes zoloft sri through just a single injection translational, industrial and commercial issues have to be addressed for example, dosing eg which drug load and particles dose zoloft sri afford therapeutic effects and the timing of treatments have to be tested synthesis schemes and reagents readily adaptable to cgmp practices should be explored zoloft sri batch to batch variations and processing choices must be minimized, whereas the synthesis yield and drug loading effectiveness must be boosted to warrant practical utility zoloft sri targeting of nanocarriers to endothelial determinants in the pulmonary vasculature promises unprecedented levels of specificity and subcellular precision of drug delivery many endothelial determinants potentially useful for drug delivery including ectoenzymes, cell adhesion molecules and caveolar antigens have been identified by methods including proteomics of endothelial plasma membrane, zoloft sri phage display libraries selections in vivo and the tracing of labeled antibodies highthroughput, discoverydriven approaches such as phage display, map vascular lumen and identify zoloft sri novel targets enriched in defined areas of the lung or endothelial domains due to a limited insight into functions of these targets, some of zoloft sri them are unlikely to have a utility for drug delivery eg due to safety concerns, yet all could be used as molecular probes in zoloft sri animal studies careful selection of targets and modulation of valency and size of the antibody directed nanocarriers help to control intracellular uptake and traffic zoloft sri of cargoes these parameters can be further finetuned, capitalizing on specific features of carriers including relatively labile protein conjugates, liposomes or polymer carriers with zoloft sri builtin rates of degradation and release, and membrane permeating moieties it is tempting to speculate that the treatment of pathologies, including but not limited to zoloft sri acute lung injury, lung transplantation, pulmonary edema, thrombosis, hypertension and inflammation, will eventually benefit from targeting the delivery of drug nanocarriers to the pulmonary zoloft sri vasculature acknowledgments this work was supported by nhlbi rol grants hl, hl and hl, department of defense grant pr and pennsylvania nti core project zoloft sri the authors thank drs s muro, m koval and v shuvaev university of pennsylvania for the exciting and stimulating discussions and advice references muzykantov zoloft sri vr delivery of antioxidant enzyme proteins to the lung antiox redox signal fishman ap a century of pulmonary hemodynamics am j respir crit care zoloft sri med pandey r, sharma a, zahoor a, sharma s, khuller gk and prasad � poly dl lactidecoglycolide nanoparticlebased inhalable sustained drug delivery system for zoloft sri experimental tuberculosis j antimicrob chemother corkery � inhalable 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