Portal Delivery

Since an iontophoresis system must be placed on the skin, it is beyond the capabfiity of this technology to provide portal delivery of insulin. This may not be a fatal flaw, however, since the recent DCCT trials have shown that intensive management of diabetes via nonportal routes can provide dramatically improved outcomes. However, a delivery system that could provide portal dehvery of insulin would be expected to provide even better results. 

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Portal delivery. In order to supply the Uver with all the insulin it needs, the pancreas delivers the insulin into the portal blood supply. Ideally, a replacement system would act similarly. 

Negotiation and collaboration in value chain operations is focused on electronic and automated exchange of orders and further business documents like as invoices, quality certificates or delivery documents using electronic shops, portals or marketplaces. 

Sinko et al. [92] established an Intestinal and Vascular Access Port (IVAP) model where dogs were fitted with three intestinal catheters for site-specific administration to various section of the intestine (i.e. duodenum, ileum, and colon), one vascular catheter for access to the portal vein, and a peripheral vein (e.g. branchial) for IV access. The animals were allowed to recover for 2 weeks prior to initiation of studies. The extent of intestinal versus hepatic first-pass metabolism was determined by comparing blood levels following intra-duodenal (AUQ.d.) versus portal (AUVi.p.v.) versus intravenous (AUQ.V.) administration. The model also lends itself to a comparison of the impact of site-specific preferential absorption, and hence a determination of the optimal site for intestinal delivery. 

Patton JS, Fishbum CS, Weers JG (2004) The lungs as a portal of entry for systemic drug delivery. Proc Am Thorac Soc 1 338-344... 

Drug molecules that have traversed the physieal and enzymatic barriers of the colonic mucosa may enter the blood-eapillary bed or the lymphatic sinuses. Intact drug that reaches the venous capillaries from the submucosa is transported to the liver via the hepatic-portal system where they may undergo significant metabolism. On the other hand, uptake into the lymphatie sinuses of the colon results in direct delivery into the systemic circulation that causes less metabolic breakdown of the absorbed drug [3]. 

Tertiary hypothyroidism, or hypothalamic hypothyroidism, results from impaired TRH stimulation of pituitary TSH. This may be due to a disorder that damages the hypothalamus or interferes with hypothalamic-pituitary portal blood flow, thereby preventing delivery of TRH to the pituitary. Tumors, trauma, radiation therapy, or infiltrative disease of the hypothalamus can cause such damage. This relatively rare form of hypothyroidism is also characterized by inappropriately low levels of serum TSH. 

Lambert et al. have explored the use of Raman spectroscopic measurements of glucose present in the aqueous humor of the eye.20,21,31 This is undoubtedly an excellent portal for optical measurements with potential advantages such as easy access and less complex fluid composition. In spite of these advantages, a spectroscopic measurement in the eye carries the risk of injury if the probing light is too intense. Therefore, dosimetry and a foolproof light delivery method are important concerns for in vivo human studies. 

Similarly, topical targeting techniques (including advanced aerosol systems and dermal or transdermal formulations) have been introduced or are about to be introduced that provide prolonged localized delivery or alternative means of systemic delivery. Both pose problems of a different kind (and perhaps magnitude), depending on whether the lungs or the skin, respectively, are the site of action or the portal of entry for systemic delivery. 

Lipids, unlike many excipients, whether present in food or as discreet pharmaceutical additives, are processed both chemically and physically within the GIT before absorption and transport into the portal blood (or mesenteric lymph). Indeed, most of the effects mediated by formulation-based lipids or the lipid content of food are mediated by means of the products of lipid digestion—molecules that may exhibit very different physicochemical and physiological properties when compared with the initial excipient or food constituent. Therefore, although administered lipids have formulation properties in their own right, many of their effects are mediated by species that are produced after transformation or activation in the GIT. An understanding of the luminal and/or enterocyte-based processing pathways of lipids and lipid systems is therefore critical to the effective design of lipid-based delivery systems. 

Fig. 1.2. Long-term expression of a rAAV2 vector after delivery to mouse liver. Aliquots of the indicated dosages of a CMV enhancer/chicken beta actin hybrid promoter-driven human alpha 1-antitrypsin (AAT)-expressing rAAV2 vector (CB-AT) or of a similar elongation factor 1-alpha promoter-driven vector (E-AT) were injected into C57B1/6 mice either by portal vein (PV) or tail vein (TV). The serum levels of human AAT were measured by ELISA serially from 0 to 52 weeks after injection, and these values are shown on the y-axis.

Peripheral intravenous delivery could essentially achieve the same vector distribution as portal vein delivery where vector genomes are primarily detected in the liver and secondarily in other tissues depending on the promoter and serotype used. Unlike portal vein delivery, tissues (other than the liver) from animals treated intravenously may be corrected by direct transduction in addition to by uptake of liver-secreted protein. Peripheral IV delivery would be preferred over portal vein delivery for clinical safety concerns. However, the antibody-mediated inhibition of circulating GAA remains a concern for both portal vein and intravenous vector delivery approaches. In effort to understand the full capacity of... 

As mentioned earlier, all subsystems of a trace portal must be integrated to facilitate explosives detection. After removal and transport of the explosive, the explosive must be collected for eventual delivery to the detector. The preconcentrator receives the explosive from the sample collection subsystem. A well-designed preconcentrator will enhance a marginal sample collection system. 

Transdermal Delivery Systems. Transdermal delivery of drugs over extended periods of time for systemic therapy has received significant attention. The importance and future prospects of this field are further reflected in the section on Transdermal and Transmucosal Delivery Systems (Chapters 17-23). Intact human skin, once thought to be an impermeable barrier, was realized as a potential portal of entry for systemic drug therapy only recently. 

Recently, there is a growing recognition that the benefits of intravenous drug infusion can be closely duplicated, without its potential hazards, by using the intact skin as the portal of drug administration to provide a continuous transdermal drug delivery into the systemic circulation Q). 

Barry NPE, Zava O, Dyson PJ, Therrien B (2011) Excellent correlation between drug release and portal size in metalla-cage drug delivery systems. Chem Eur J 17 9669-9677... 

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