Poly paclitaxel conjugate

Li, C. Yu, D.-R Newman, R. A. Cabral, P. Stephens, L. C. Milas, L. Wallace, S. Complete regression of well-established tumors using a novel water-soluble poly(L-glutamic acid)-paclitaxel conjugate. Cancer Res., 1998, 58 2404—2409. 

Being the first poly(glutamic acid) conjugate tested in clinical trials, paclitaxel conjugate of poly(glutamic acid) (CT-2103) was observed to have superior antitumor activity to free paclitaxel. In preclinical studies, it was evidenced that the whole conjugate extravasated to the tumor site and the drug was released extracellularly in... 

OPAXIO, Poly(L-Glutantic Acid)-Paclitaxel Conjugates... 

E. Oldham, C. Li, S. Ke, S. Wallace, P. Huang, Comparison of action of paclitaxel and poly (L-glutamic acid)-paclitaxel conjugate in human breast cancer cells, Int. J. Oncol. 16 (2000) 125—132. 

C. Chamsangavej, and S. Wallace. 2000. Biodistribution of paclitaxel and poly(L-glutamic acid)-paclitaxel conjugate in mice with ovarian OCa-1 tumour. Cancer Chemother.Pharmacol. 46 416-422. 

Singer, J. W., de Vries, P., Kumar, A., Baker, B., Lyim, S., Li, C., and Wallace, S. Poly-L-Glutamic Acid Paclitaxel Conjugate (PG-TXL) A water-soluble biodegradable conjugate with decreased toxicity and enhanced efficacy. 4th International Symposium on Polymer Therapeutics. 2000. 

D., Main, M., Brannan, M. D., Elliott, S., Verrill, M., and Calvert, H. Phase 1 and pharmacological study of CT-2103, a poly(L-glutamic acid)-paclitaxel conjugate. 

Polymeric micelles formed by Pluronics, PEG phospholipid conjugates, PEG-b-polyesters, or PEG-b-poly-L-amino acids were proposed for drug delivery of poorly water-soluble compounds, such as amphotericin B, propofol, paclitaxel, and photosensitizers [77,86,87]. It was also emphasized that using polymeric micelles can significantly increase the drug transport into the brain. 

Rendri, A. Conover, C. D. Greenwald, R. B. Antitumor activity of paclitaxel-2 -glycinate conjugated to poly(ethylene glycol) a water-soluble prodrug. Anti-Cancer Drug Des., 1998, 13 387-395. 

Conjugation to poly(ethylene glycol) (PEG), or PEGylation, is a well-established approach in protein stabilization (which is described in Section 8.2.3). PEGylation can also be used to increase the water solubility of drugs. For example, conjugation to PEG increases the aqueous solubility of paclitaxel and its derivatives [4] (Table 8.2 and Figme 8.2). The increase in solubility is... 

Li C, Ke S, Wu QP, Tansey W, Hunter N, Buchmiller LM, Milas L, Chamsangavej C, Wallace S. Tumor irradiation enhances the tumor-specific distribution of poly(L-glutamic acid)-conjugated paclitaxel and its antitumor efficacy. Clin Cancer Res 2000 6 2829-2834. 

Lewis et al. were able to form bioconjugates using a bis-sulfone polymer. Conjugation of NHS end-functionalized 2-methacryloyloxyethyl phosphorylcho-line (MPC) to interferon (IFN)-a2a was unsuccessful, so a different route to create bioconjugates was required. Poly MPC has been used in a wide range of biomedical applications, notably in the solubilization of drugs such as paclitaxel and amphotericin A bis-sulfide initiator... 

SMANCS Poly(styrene-co-maleic acid-half-n-butylate) conjugated with neocarzinostatin Tax Paclitaxel, also known as Taxol... 

Poly-(L)-Glutamic Acid-Paclitaxel (CT-2103) [XYOTAXT , a Biodegradable Polymeric Drug Conjugate... 

The present report describes the covalent conjugation of paclitaxel to y-carboxylic acids of poly-L-glutamic (PG) acid (CT-2103). Paclitaxel is a particularly appropriate molecule for conjugation to a polymer carrier because it is broadly active as an anti-tumour agent, yet it is difficult to deliver because it is highly hydrophobic. The commercial preparations of pacKtaxel use Cremophor and ethanol as solubilising agents. These have inherent toxicities and require slow infusions and premedications with corticosteroids and histamine receptor blockers. 

The molecular formula of CT-2103 is a distribution since the a-poly-(L)-glutamic acid degree of polymerization and the number of conjugation sites with paclitaxel are variable. A generalized molecular formula is shown. 

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