Intraarterial delivery

Embolization involves the deliberate occlusion of the arterial supply to the tumor to create ischemia, tumor necrosis, and to arrest growth by the intraarterial delivery of particulate materials, sclerosing solutions and substances introduced in a liquid state that eventually solidify or precipitate. This concept was first described in 1960 by Dawbain et al, who injected melted paraffin-petrolatum into an external carotid artery in a patient with head and neck cancer. It wasn t until the early 1970s that catheter technology improved to the degree for transcatheter embolotherapy to emerge. 

In an effort to overcome the lack of solubility, poor penetration across the blood-brain barrier and decreased delivery of conventional systemic agents by a compromised intratumoral blood supply, several studies have evaluated various combinations of BCNU alone or with other agents delivered intraarterally. Unfortunately, response rates and median survival times observed in patients treated with intraarterial chemotherapy have not been significantly different than those seen in patients treated with standard intravenous nitrosurea-containing regimens, while increased rates of toxicity such as leukoen-cephalopathy, retinal injury, edema, myelosuppression, sepsis, and thrombotic complications have been noted (40-46). 

In addition to the usual intravenous or oral routes, some anticancer agents have been administered by regional intraarterial perfusion to increase drug delivery to the tumor itself and at the same time diminish systemic toxicity. Thus, patients with metastatic carcinomas of the liver and little or no disease elsewhere (a common occurrence in colorectal cancer) can be treated with a continuous infusion of fluorouracil or floxuridine through a catheter implanted in the hepatic artery. 

Parenteral delivery routes are those that do not give rise to drug absorption into the splanchnic circulation. Thus, they avoid the possibility of hepatic first-pass metabolism. It should be noted that some parenteral routes do not avoid other first-pass metabolism effects (e.g., pleural metabolism for some inhaled drugs). Some major parenteral drug delivery routes are intraarterial, intrathecal, intravenous, intramuscular, trans-dermal, intranasal, buccal, inhalation, intraperitoneal, vaginal, and rectal. 

Fortin D, Desjardins A, Benko A, Niyonsega T, Boudrias M. Enhanced chemotherapy delivery by intraarterial infusion and blood-brain barrier disruption in malignant brain tumors the Sherbrooke experience. Cancer 2005 103 2606-2615. 

The delivery of radioactive isotopes via vascular-borne microparticles to internal tumors dates back to 1947 when Muller and Rossier infused Zn and Au to treat renal cell metastases to the lungs, previously irradiated for bronchial carcinoma. Radioactive carbon particles that were used were 40-50 pm in diameter and were successfully trapped in bronchial tumors [1,2]. Di Matteo reported the most extensive experience using Au particles delivered by intraarterial injection to treat lung carcinoma, but subsequently abandoned this approach in favor of microsphere therapy [3]. Although most clinical experience is with °Y, a variety of solid tumors have been treated with intraarterial particles suspended in solution as the therapeutic isotope [4-6],... 

An Y, Hubbell JA. Intraarterial protein delivery via intimally-adherent bilayer hydrogels. J Control Release 2000 64(l-3) 205. 

Vascular Anatomy The delivery of intraarterial chemotherapeutic agents requires the operator to be knowledgeable of the normal and variant vascular anatomy to perform selective and superselective arterial catheterizations. These maneuvers can be facilitated by the use of single end-hole or multi-sidehole microinfusion catheters and wires. The use of multi-sidehole catheters prevents the inadvertent catheterization and infusion of a small undesirable side branch that may increase local toxicity. This is particularly useful for extremity infusion to reduce the incidence of chemodermatitis. 

Recent development of a new PVA hydrogel bead has enabled accurate doxorubicin loadings to be achieved, with subsequent slow first order release. This novel drug-delivery system has been recently evaluated for intraarterial treatment of hepatic lesions [22], Doxorubicin-eluting beads (DC Bead for loading by the physician and PRECISION Bead preloaded with doxorubicin. Biocompatibles UK Ltd, Surrey, UK), are designed for intraarterial infusion and selective tumor targeting [14],... 

Geschwind JF, Khwaja A, Hong K (2005) New intraarterial drug delivery system Pharmacokinetics and tumor response in an animal model of liver cancer. 2005 ASCO Annual Meeting, Orlando, Florida. 

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