Complete regression of xenografted human carcinomas by a paclitaxel–carboxymethyl dextran conjugate (AZ10992)

Development, Optimization and Absorption Mechanism of DHP107, Oral Paclitaxel Formulation for Single-Agent Anticancer Therapy

“…This particular component is known to cause hypersensitivity (Weiss et al, 1990), to be responsible for nonlinear pharmacokinetic behavior and to cause paclitaxel precipitation oftentimes when diluted during the infusion process (Pfeifer, 1993). Formulations for paclitaxel and its analogs have been prepared in many different ways for various administration procedures (Kim et al, 2006;Xie et al, 2007;Sugahara et al, 2007;Singla et al, 2002;Hennenfent & Govindan, 2006). Several years ago, Abraxane ® , a suspension of albumin nanoparticles containing paclitaxel, obtained approval to treat metastatic breast cancer patients (Ibrahim et al, 2002;Garber, 2004 Surfactant mix + KR30031 (5) 0.39 (0-12) 0.06 5 rat Kim et al, 2004 Suspension in Tween 80 + quercetin (20) 5.00 (0-24) 0.28 40 rat Choi et al, 2004b Taxol+cyclosporine A (50) 3.61 (0-4) 0.82*** 10 mice Bardelmeijer et al, 2004 Taxol+PSC 833 (50) 2.71 (0-4) 1.47*** 10 mice Bardelmeijer et al, 2004 Taxol+GF120918 (25) 1.39 (0-4) 0.55*** 10 mice Bardelmeijer et al, 2004 Taxol+LY335979 (80) 1.41 (0-4) 0.42*** 10 mice Bardelmeijer et al, 2004 Taxol+R101933 (80) 0.93 (0-4) 0.32*** 10 mice Bardelmeijer et al, 2004 Taxol+GF120918 (25) 2.65 (0-10) 0.77 10 mice Bardelmeijer et al, 2000 Taxol+PSC 833 (50) mice Asperen et al, 1997 * Time-interval used for the calibration of AUC, ** Dose of the inhibitor in mg/kg, and *** Estimated concentration Table 1.…”

Dextran-b-poly(L-histidine) copolymer nanoparticles for pH-responsive drug delivery to tumor cells

“…32 Further, in an in vivo study, HT-29 colorectal tumor xenografts regressed completely in response to intravenous administration of a dextran-paclitaxel conjugate. 33 Therefore, DexPHS block copolymers can be used as a fully biocompatible material for drug delivery. DexPHS block copolymer nanoparticles showed pH-responsive changes in particle size and drug release, ie, their size and drug release rate was increased at acidic pH.…”

Poly (L-glutamic acid)-Paclitaxel Conjugates for Cancer Treatment

“…The clinical use of PTX also leads to many side effects. Side effects of PTX include nausea, vomiting, diarrhea, mucositis, myelosuppression, cardiotoxicity, neurotoxicity and hypersensitivity reactions, and the latter two are mainly owing to polyoxyethylated castor oil (Cremophor ® EL) and ethanol used for solubilizing PTX (Rogers, 1993;Sugahara et al, 2007). PTX for injection is supplied in 50% Cremophor ® EL and 50% dehydrated ethanol.…”

“…These delivery systems are able to provide enhanced therapeutic efficacy and reduce toxicity of anticancer agents mainly by altering the pharmacokinetics and biodistribution of the drugs (Kim & Lim, 2002). The idea is attractive and could form the basis of a new generation of anticancer agents (Sugahara et al, 2007). Many polymers have been investigated as carriers for conjugates, including poly(glutamic acid), poly(L-lysine), poly(malic acid), poly(aspartamides), poly((N-hydroxyethyl)-L glutamine), poly(ethylene glycol), poly(styrene-co-maleic acid/anhydride), poly (N-(2-hydroxypropyl) methacrylamide) copolymer, poly(ethyleneimine), poly(acroloylmorpholine), poly(vinylpyrrolidone), poly(vinylalcohol), poly(amidoamines), divinylethermaleic anhydride/acid copolymer, dextran, pullulan, mannan, dextrin, chitosan, hyaluronic acid and proteins etc.. Coupling low molecular weight anticancer drugs to high or low molecular weight polymers is an effective method for improving the therapeutic index of clinically used agents.…”