![]() ![]() However, its clinical trials also revealed an increased peripheral neuropathy as compared to Taxol. ![]() Taxol such as increased antitumor activity and tumor accumulation in several mice xenograft models, significantly higher maximum tolerated doses (MTD) in human, as well as approximately 74% increase of response rates in metastatic breast cancer patients ultimately led to the clinical approval of this new formulation. ![]() The clinical demand for alternative formulations led to the development of Abraxane, a nanoparticle formulation (hydrodynamic diameter ≈ 130 nm) comprising human serum albumin and ca. Cremophor EL causes severe allergic, hypersensitivity, anaphylactic reactions and nephro- and neurotoxicity in animals and humans, which significantly limits dosing and requires clinical intervention. Excipient plasma concentration can reach 0.4% (v/v) and persist above 0.1% (v/v) for over 24 hours. It is characterized by very low drug loading (1% wt.), thus, the amount of the excipient, Cremophor EL/ethanol, necessary to deliver effective doses of PTX is substantial. The first clinical formulation of PTX was Taxol. Both are blockbusters and make PTX the best selling chemotherapeutic in history. Three formulations are currently clinically approved, two of which by the FDA. Apart from excellent potency, PTX is characterized by an extremely low solubility in aqueous media (<1 mg/L), thereby demanding delivery vehicles for parenteral administration. By interfering with tubulin polymerization, thus perturbing microtubule dynamics, PTX leads to chromosome missegregation on multipolar spindles. ![]() Paclitaxel (PTX) is a powerful antineoplastic agent against metastatic breast cancer, non-small cell lung cancer, advanced ovarian cancer, head and neck cancer and other malignancies. The promising preclinical data on the presented PTX nanoformulation showcase the need to investigate new excipients and is a robust basis to translate into clinical trials. As a result, we observed improved therapeutic outcome in orthotopic tumor models including particularly faithful and aggressive “T11” mouse claudin-low breast cancer orthotopic, syngeneic transplants. Pharmacokinetic analysis reveals that the higher dose administered leads to a higher exposure of the tumor to PTX. We observe favorable in vitro and in vivo safety profiles and a higher maximum tolerated dose compared to clinically approved formulations. and PTX solubility of up to 45 g/L, excellent shelf stability and controllable, sub-100 nm size. Here, we present translational evaluation of a nanoformulation of PTX, which is characterized by a facile preparation, extraordinary high drug loading of 50 % wt. The poor solubility of paclitaxel (PTX), the commercially most successful anticancer drug, has long been hampering the development of suitable formulations. I mean IM doing realy good and then a survivor goes through a window and I litterly POOP myself in anger! I mean what am I suppose to DO someone PLEASE tell I mean I"m looking at him crouching over and over again on the otherside of the window while the other players turn on generator after generator SOOOO BAD the players that do this are just bad and they should be PREMA BANNED. " Now that I have your attention, the problems with this game! I hate that when I'm doing SUPER well I get caught first and then camped on the hook and even though I'm waving my arms for help.no one comes! This is super UNFAIR and I think the other players should be forced to come and help! Also when I"M a killer I don't have any fun because of all THE CHEESE SO MUCH CHEESE its like a CHEESE PIZZA with EXTRA EXTRA CHEESE. ![]()
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