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 bromocriptine cocaine using carriers of adequate size for example, nanocarriers based on polylactic glycolic acid polymer, accepted for human use for macroimplants, may degrade into lactic bromocriptine cocaine acid and glycolic acid within the target cells, potentially exceeding its metabolic potential potentially harmful effects of activation systemic defense systems ie complement, cytokines, bromocriptine cocaine 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 bromocriptine cocaine through just a single injection translational, industrial and commercial issues have to be addressed for example, dosing eg which drug load and particles dose bromocriptine cocaine afford therapeutic effects and the timing of treatments have to be tested synthesis schemes and reagents readily adaptable to cgmp practices should be explored bromocriptine cocaine 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 bromocriptine cocaine 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, bromocriptine cocaine phage display libraries selections in vivo and the tracing of labeled antibodies highthroughput, discoverydriven approaches such as phage display, map vascular lumen and identify novel targets enriched in defined areas of the lung or endothelial domains due to a limited insight into functions of these targets, some of bromocriptine cocaine them are unlikely to have a utility for drug delivery eg due to safety concerns, yet all could be used as molecular probes in bromocriptine cocaine animal studies careful selection of targets and modulation of valency and size of the antibody directed nanocarriers help to control intracellular uptake and traffic bromocriptine cocaine of cargoes these parameters can be further finetuned, capitalizing on specific features of carriers including relatively labile protein conjugates, liposomes or polymer carriers with bromocriptine cocaine 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 bromocriptine cocaine acute lung injury, lung transplantation, pulmonary edema, thrombosis, hypertension and inflammation, will eventually benefit from targeting the delivery of drug nanocarriers to the pulmonary bromocriptine cocaine vasculature acknowledgments this work was supported by nhlbi rol grants hl, hl and hl, department of defense grant pr and pennsylvania nti core project bromocriptine cocaine the authors thank drs s muro, m koval and v shuvaev university of pennsylvania for the exciting and stimulating discussions and advice references muzykantov bromocriptine cocaine vr delivery of antioxidant enzyme proteins to the lung antiox redox signal fishman ap a century of pulmonary hemodynamics am j respir crit care med pandey r, sharma a, zahoor a, sharma s, khuller gk and prasad � poly dl 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