Polymer anticancer agents

Classical or conventional pharmaceutical agents in combination with lactide/glycolide polymers have been widely studied since about 1973. In general, these compounds are bioactive agents usually produced by synthetic chemistry, with molecular weights of less than a few hundred and relatively stable structures. Examples include steroid hormones, antibiotics, narcotic antagonists, anticancer agents, and anesthetics. 

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. 

Matsumura Y, Kataoka K (2009) Preclinical and clinical studies of anticancer agent-incorporating polymer micelles. Cancer Sci 100 572-579... 

An additional opportunity that arises from applying polymer-based materials is the preparation of water-dispersible composites, which is an essential feature for biomedical purposes, as it is possible to attach bio-active molecules to the poly-mer/CNTs systems and specifically deliver them to cells. In this manner, plasmid DNA, siRNA (Fig. 3.11) and several anticancer agents have been successfully bound and delivered [61]. The stratagem to generate materials with good solubility in aqueous media usually involves the presence of water-soluble polar groups (e.g. phosphates, protonated amines etc.) embedded in the polymer chain. 

Maeda, H., Seymour L. W., and Miyamoto, Y. Conjugates of anticancer agents and polymers advantages of macromolecular therapeutics in vivo. Bioconjugate Chem., 1992, 3, 351-361. 

SMANCS (Styrere-co-maleic acid/anhydride polymer bound to neocarzinostatin Neocarzinostatin (an antitumor protein) Amide bond between polymer carboxyl and protein amino None N/A SMANCS showed anticancer activity against many tumor cell lines, and had lower IC50 values than five other anticancer agents tested Liver tumors reduced more than 50% after 6 months in human subjects 15, 56, 57... 

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. 

Antimitotic drugs that target microtubules (MT) or its constituent protein tubulin are one of the most successful classes of anticancer agents discovered so far. MT are long, filamentous, tube-shaped protein polymers that are essential in all eukaryotic cells. Antimitotic agents are compounds that arrest cells in mitosis, which results in the slowing or blocking of mitosis and induction of apoptotic cell death. 

New functions can be obtained by modifications of SLNs. Incorporation of Tween 80 and Poloxamer 188 can stabilize SLNs to achieve long-circulating or crossing blood-brain barrier effects [112], Recently, novel nanoparticles called polymer-lipid hybrid nanoparticles (PLNs) were developed [113]. They can entrap cationic anticancer agents (e.g., doxorubicin) effectively by incorporation of an anionic lipophilic polymer into lipids to treat multidrug-resistant (MDR) cancers. 

The polymer formulations containing anticancer agents (paclitaxel and cis-platin) were evaluated in vivo in heterotrophic (mouse bladder tumor) and orphotrophic (rat prostate cancer) models. Single administration of polymer-pactlitaxel formulation intratumorally in a mouse bladder tumor model increased the survival rate of the animals compared to untreated animals and to animals treated with paclitaxel dispersion (conventional administration method) (27). The optimal load of paclitaxel in the polymer was established as 10% w/w. Mice treated with this formulation showed median survival rate (MSR) of... 

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