Intravenous delivery

Intravenous delivery to lungs of antiallergic compounds Sodium cromoglicate (Cromolyn sodium)... 

Intravenous delivery to lung renal artery delivery Doxorubicin... 

Since the design of the first targeted polyplexes more than 20 years ago [97, 134], numerous efforts have been made to develop polyplexes for use in medical products, both in pharmacological animal studies and in human studies. Therapeutic modalities include ex vivo treatment of isolated human patient cells, localized in vivo treatments, and - currently the most challenging delivery scenario - in vivo targeted intravenous delivery. 

Systemic targeting of pDNA and siRNA polyplexes has been demonstrated in several animal models. In continuation of the work with localized antiproliferative and immunostimulatory poly(I C) RNA, intravenous systemic delivery of EGER-targeted PEG-modified polyplexes were successfully used for human carcinoma treatment in mice [225]. The therapeutic effect was most pronounced when intravenous delivery of poly(I C) polyplexes was followed by intraperitoneal injection of peripheral blood mononuclear cells [226]. This induced the complete cure of SCID mice with pre-established disseminated EGFR-overexpressing tumors, without adverse toxic effects. Due to the chemokines produced by the internalized poly (I C) in the tumor cells, the immune cells home to the tumors of the treated animal and contribute to the tumor destruction. 

Even if a medication is available in multiple formulations and dosage forms, the prescriber must consider the absorption and distribution differences between adult and pediatric patients. Blood supply at injection or infusion site, available blood supply for unit muscle mass, and skeletal muscle mass relative to body mass vary with patient age and size, causing drug absorption to vary, as well. A rapid intravenous bolus in a pediatric patient might result in acute toxicity a slow intravenous infusion, often required in neonates, can cause erratic, unreliable drug delivery in an older child. In addition, the volume of fluid tolerated for intravenous delivery varies significantly with the age and size of the patient. The blood supply and blood flow to and from the injection site are of prime importance since a gradual decrease in blood supply per unit muscle mass is seen with maturation. In addition, the skeletal muscle mass relative to... 

Because the drug is rapidly cleared from the body, it requires continuous intravenous delivery. ... 

Yuen, P. H., Denman, S. L., Sokoloski, T. D., and Burkman, A. M. (1979), Loss of nitroglycerin from aqueous solution into plastic intravenous delivery systems. I. Pharm. Sci., 68,1163-1166. 

Goula, D., Benoist, C., Mantero, S., et al. Polyethylenimine-based intravenous delivery of transgenes to mouse lung. Gene Ther. 5 1291-1295, 1998. 

Intravenous delivery is the most direct route into the circulatory system. The entirety of the administered drug reaches the blood because the dose is placed into a vein, and therefore IV routes define 100% bioavailability. Absorption is not an issue. 

Polyethylenimine-based intravenous delivery of transgenes to mouse lung. 

Although many areas of nanotechnology do not directly deal with colloidal dispersions (such as nanoelectronic devices [952]) other areas do, such as the use of colloidal ink dispersions in robocasting to build near-nanometre scale three-dimensional structures. The possible use of nanoemulsions for intravenous delivery and in medical diagnostics has already been mentioned in Sections 14.4 and 14.5. Some other application areas include ... 

Studies have demonstrated that AAV serotypes 1 and 2 are able to efficiently transduce the murine heart for up to 10 months following GFP transgene delivery (Du et al., 2004). Recently, we have found that intravenous delivery to the neonatal mouse of the newly characterized AAV serotype 9 results in /i-galactosidase expression levels that are up to 50-fold higher in cardiac tissue than those obtained using AAV1 (Fig. 9.1) (Pacak, submitted 2004). The... 

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... 

Before reaching the target organ, drugs must pass through the liver. This can be avoided by direct intravenous delivery of drugs. Optimized oral or rectal delivery also avoids the liver passage. 

E.A. Kowaluk, et al., Interactions between drugs and intravenous delivery systems. Am. J. Hosp. Pharmacol. 39 460-467, 1982. 

Allwood MC. 1983. Sorption of drugs to intravenous delivery systems. Pharm. Int. 4(4) ... 

For intravenous delivery the ratio of ACC(deAcDIL)/AUC(DIL) is approximately 0.2 while this ratio is 0.8 for oral delivery. This difference reflects the extensive first-pass effect. Topical delivery is intermediate between the two routes and the ratios are 0.3 and 0.5 for intact and stripped skin, respectively. This suggest that there may be some first-pass metabolism by the skin. The differences between intact and stripped skin are not clearly understood but could be related nonlinear pharmcokinetics. 

Toxicology of the methylated derivatives has not been studied extensively. The LD50 for oral administration of dimethyl (3-cyclodextrin is >300mg/Kg and >200mg/Kg for intravenous administration in mice.65 Methylated derivatives interact with cellular membranes, extracting cholesterol and disrupting the membranes. This has limited interest in the derivatives for intravenous delivery of pharmaceuticals, but there has been some interest in use of methylated derivatives to enhance transdermal administration of drugs.66... 

Absorption is the transfer of a drug from its site of administration to the blood stream. The rate and efficiency of absorption depend on the route of administration. For intravenous delivery, absorption is complete, that is, the total dose of drug reaches the systemic circulation. Drug delivery by other routes may result in only partial absorption and thus lower bioavailability. For example, the oral route requires that a drug dissolve in the gastrointestinal fluid and then penetrate the epithelial cells of the intestinal mucosa disease states or the presence of food may affect this process. 

Lee MD, Hess MM, Boucher BA, Apple AM. Stability of amphotericin B in 5% dextrose injection stored at 4 or 25°C for 120 hours. Am J Hosp Pharm 1994 51 394-396. Kowaluk EA, Roberts MS, Polack AE. Interactions between drugs and intravenous delivery systems. Am J Hosp Pharm 1982 39 460 67. 

The present drug of choice for this purpose is cis-platin [cis-diamminedichloroplatinum (II)], or its analog carboplatin. As will be discussed in Chapter 30, early compartmental models predicted a substantial pharmacokinetic advantage of intraperitoneal over intravenous delivery (8). A later Phase III trial (7) confirmed that a comparative survival advantage... 

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