PEG-paclitaxel

Poly(triazine) G2 PEG Paclitaxel Ester or ester- Cancer No Yes Yes 349... 

Several highly water-soluble PEG esters of paclitaxel were prepared and studied by Enzon Inc. researchers. They proved to function as prodrags, that is, their breakdown occurred in a predictable manner. Although a PEG-paclitaxel derivative... 

Since the discovery of vesicular structures, termed liposomes, by Alec Bangham, a tremendous amount of work on applications of liposomes has emerged. The use of small unilamellar liposomes as carriers of drugs for therapeutic applications has become one of the major fields in liposome research. The majority of these applications are based on the encapsulation of water-soluble molecules within the trapped volume of the liposomes. Long circulating poly(ethylene glycol) (PEG) modified liposomes with cytotoxic drugs doxorubicin, paclitaxel, vincristine, and lurtotecan are examples of clinically applied chemotherapeutic liposome formulations (1,2). 

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. 

PEG 300 on paclitaxel transport was observed. It was concluded that the efflux pump inhibition mechanism of PEG 300 was mediated by changes in the microenvironment of Caco-2 cell membranes (Hugger et al. 2002). These changes are probably related to modifications in the fluidity of the polar head group regions of cell membranes. 

A phase III study was conducted to compare PEG-liposomal DXR (50 mg/m2 every 4 weeks) with paclitaxel (175 mg/m2 every 3 weeks) using 214 patients with relapse after first-line platinum-based chemotherapy [420], As previously, the response rates and PFS were not significantly different, but again the liposomal formulation was notably less toxic as fewer patients recorded with grade 4 adverse effects (17% compared to 71% for topotecan) and thus was more tolerable. 

Folate-PEG-modified prodmgs of paclitaxel were recently prepared. Although the selected prodrug taxol-7-PEG-folate increased the survival in mice, it was not better than paclitaxel. ... 

PEG-liposomes DOX, paclitaxel, cisplatin Passive Clinical use, Phase Phase 1/11 ... 

PEG-PAsp (4-phenyl-1-butanol substituted Paclitaxel Passive Colon 26 tumor-bearing CDFl mice ... 

PEG-coated (polycyanoacrylate) nanoparticles Paclitaxel Transferrin S-180 bearing mice ... 

Yan, Z. Li, Y. In vitro and in vivo evaluation of actively targetable nanoparticles for paclitaxel delivery PEG coated... 

Ruan, G. Feng, S.-S. Preparation and characterization of poly(lactic acid)-poly(ethylene glycol)-poly(lactic acid) (PLA-PEG-PLA) microspheres for controlled release of paclitaxel. Biomaterials 2003, 24, 5037-5044. 

Fig. 1 Fluorescence microscopy of the binding of Rh-PE-labeled paclitaxel-loaded poly(ethylene glycol)-phosphatidyl ethanolamine (PEG-PE)-based micelles to murine EL4 and large luteal cells (LLC) and human BT-20 and MCF-7 cells. (With permission from Ref. l)...

The solid dispersion method (Fig. 2B) was used for solubilization of paclitaxel into PEG-poly(D,L-lactide) diblock copolymer micelles. Paclitaxel and the polymer were dissolved in acetonitrile followed by evaporation of the solvent under a stream of nitrogen at 60°C to obtain a gel-like polymer-drug matrix. Dissolution of the solid matrix in water at about 60° C with stirring led to formation of drug-loaded micelles. Because a heating is needed to completely dissolve the polymer-drug matrix, this method may not be not desirable for thermally unstable drugs. 

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