Anticancer agents delivery

Block copolymer micelle formulations of doxorubicin and paclitaxel are both in Phase l/ll trials for the treatment of advanced cancers. Aliabadi and Lavasanifar (2006) recently compiled a review of the clinical status of polymeric micelle systems for anticancer agent delivery. 

Liposomal formulations, type of tumor, anticancer agent, delivery pathway, day of treatment, and general conclusions are given in Table 6. DaunoXome (liposomal daunorubicin) and Doxil (liposomal doxorubicin) have been proved to have good response in clinical trials, in the range of approximately 40%. 

Strobel et al. (101) reported a unique approach to delivery of anticancer agents from lactide/glycolide polymers. The concept is based on the combination of misonidazole or adriamycin-releasing devices with radiation therapy or hyperthermia. Prototype devices consisted of orthodontic wire or sutures dip-coated with drug and polymeric excipient. The device was designed to be inserted through a catheter directly into a brain tumor. In vitro release studies showed the expected first-order release kinetics on the monolithic devices. 

H., and Muranishi, S., Lactic acid oligomer microspheres containing an anticancer agent for selective lymphatic delivery. 

Low-density lipoprotein 0.017-0.025 Delivery to neoplastic cells Methotrexate, anticancer agents... 

These amino acid and protein binding results might account for the low toxic side effects of this class of anticancer agents (72). On the other hand, the relatively weak binding to amino acids and proteins could perhaps aid in transport and delivery of active species to cancer cells prior to binding to DNA or RNA (75). 

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. 

In summary, the results obtained so far and reviewed here bode well for the future of polymers in the delivery of anticancer agents. A further systematic study of their advantages and limitations is necessary to evaluate fully their therapeutic potential. The final judgement, however, will come from the results of clinical trials. 

Liu, J., Y.Xiao, andC. Allen. 2003. Polymer-drug compatibility aguidetothe development of delivery systems for the anticancer agent, ellipticinA. Pharm. Sci93 132-143. 

Immunoliposomes have specific antibodies or antibody fragments on their surface to enhance target site binding. The primary focus of their use has been in the targeted delivery of anticancer agents. 

If the compound requires delivery to a particular site or organ to obtain the desired pharmacology, such as into the brain for CNS activity or into a tumor for an anticancer agent, preliminary drug metabolism studies can be conducted to demonstrate that the candidate is being delivered to the site of action and that the extent and duration of delivery are sufficient to provide the desired pharmacology. 

As mentioned earlier, the s.c. route for delivery of anticancer agents could prevent the metastatic spread of tumors that occurs often through the lymphatic system. However, a number of limiting factors, such as incomplete absorption of drug-loaded liposomes, which would increase, for example, the toxicity of the released drug at the surrounding tissue and the development of tumors in the regional lymph nodes could limit the therapeutic potential of liposomes. 

Vaccari, L., et al. (2006), Porous silicon as drug carrier for controlled delivery of doxorubicin anticancer agent, Microelectron. Eng., 83(4-9), 1598-1601. 

Tumor-Speckle MAbs or Fragments. In recent years, MAbs have been identified as effective anticancer agents. Several MAbs have been approved for clinical uses since 1997, and many more are in clinical trials. MAbs are believed to have multifunctional mechanisms. Their high selectivity toward tumors makes them ideal targeting ligands for actively tumor-targeted drug delivery systems. 

The small intestine is drained by the hepatic portal vein, making the liver the first port of call for orally absorbed drugs. Therefore, high hepatic metabolism will compromise systemic availability. Formulation to enhance lymphatic absorption offers the potential for avoiding such first-pass metabolism. It could also target anticancer agents to lymphatic carcinomas. Table 1 lists various materials and associated therapeutic agents that have been formulated for lymphatic delivery. 

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