Site-specific targeting

Poste, G., and Kirsh, R. (1983). Site-specific (targeted) drug delivery in cancer chemotherapy. Biotechnology, 1, 869-878. 

Provide a specific interaction between the delivery and biological systems such as site-specific targeting, regional delivery, or localized delivery to improve the therapeutic index of a drug. 

The success of treating tumours, especially solid tumours, by systemic therapy depends on various characteristics of the tumour. Besides the importance of intrinsic drug activity and the potential targets within the tumour cells, drug pharmacokinetics and whole body distribution, site of delivery and the ability of site-specific targeting (affinity) are important features. 

Transcoronary venous injection is performed with a catheter system threaded percutaneously into the coronary sinus. Initial studies in swine have confirmed the feasibility and safety of this approach [121]. This delivery method has also been used to deliver skeletal myoblasts to scarred myocardium in cardiomyopathy patients [120]. With intravascular ultrasound guidance, this approach allows the operator to extend a catheter and needle away from the pericardial space and coronary artery into the adjacent myocardium. To date, human feasibility studies have had a good safety profile. This technique is limited, however, by coronary venous tortuosity, lack of site specific targeting, and its own technically challenging nature. Unlike the transendocardial approach, in which cells are... 

Molecular parasites may also have originated in an RNA world. With the appearance of the first inefficient self-replicators, transposition could have been a potentially important alternative to replication as a strategy for successful reproduction and survival. Early parasitic RNAs would simply hop into a self-replicating molecule via catalyzed transesterification, then passively undergo replication. Natural selection would have driven transposition to become site-specific, targeting sequences that did not interfere with the catalytic activities of the... 

Yun YH, Goetz DJ, Yellen P et al (2004) Hyaluronan microspheres for sustained gene delivery and site-specific targeting. Biomaterials 25(1) 147-157... 

Inhalation therapy is gaining importance in the therapy of a number of pulmonary diseases. This site-specific targeted delivery aims to achieve high local activity with reduced systemic side effects. 

The toxic effect of many xenobiotic compounds in the kidneys is specific to the anatomical locations, i.e. proximal tubules, glomeruli, medulla/papilla, or loop of Henle. The site-selective injury observed in humans when exposed to many compounds is similar to that in domestic animals. The cause of these site-specific target injuries is multifactorial and may include detoxification mechanisms, regenerative ability, difference in blood flow, and transport and accumulation of the chemicals and their metabolites. 

Tier 2 produces site-specific target levels (SSTLs) that are protective of human health and the environment, but utilizes more site-specific data than Tier 1. This level of sophistication should address 70-80% of the sites. This more site-specific assessment involves the assumption of reasonable use exposure assumptions, considers actual beneficial uses of resources, and provides a tool for determining points of compliance. 

When the drug candidate is being developed for site-specific targeted delivery... 

Overall 30 of the 39 targets set for 1998 were achieved. Later in this commentary (except for the companywide target for accidents) site-specific targets will only be used as examples when discussing environmental indicators. 

Protein targeting to both mitochondria and chloroplasts Involves the sorting of proteins to multiple sites within the respective organelle. Briefly list these sites. Taking the mitochondrion as an example and the proteins ADP/ATP antiporter and cytochrome b2 as the specific cases, compare and contrast the extent to which a common mechanism Is used for the site-specific targeting of these two proteins. 

To identify necessary response actions, each complete exposure pathway can be analyzed on a site-specific basis to evaluate the potential for exposure in excess of safe levels. For the purpose of this evaluation, Site-Specific Target Levels (SSTLs) can be derived for relevant exposure pathways, receptors, and constituents of concern and compared to measured source media concentrations. Source media exceeding these target levels will require remedial action in a timeframe necessary to control exposure. 

Site-Specific Target Level For a given exposure pathway and contaminant, the SSTL represents a concentration in the affected source medium (soil, groundwater, surface water, or sediment) that is protective of a human or ecological receptor located at a relevant point of exposure (POE). For example, for the human health soil-to-air exposure pathway, the SSTL is the mean concentration in the affected surface soil zone that will prevent unsafe human exposures via vapour or particulate release to air. For each... 

Ligands attached to the surface of the spheres facilitate site-specific targeting. Different routes of administration, including oral, nasal, parenteral. 

Some establishments selected for inspection under the SVEP may also fall under one or more other OSHA initiatives such as Site-Specific Targeting (SST) or Local Emphasis Programs (LEP). Inspections under these programs may be conducted either separately or concurrently with inspections under this Instruction. 

---