Antitumor drugs release

Controlled-release technology based on the external temperature-activated release can find application in diverse industrial fields. In the pharmaceutical area, for example, the deviation of the body temperature from the normal temperature (37°C) in the physiological presence of the pathogens or pyrogens can be utilized as a useful stimulus that induces the release of the therapeutic agents from a thermosensitive controlled-release system. Physically controlled temperature using a heat source such as the microwaves from outside the body can also be used for temperature-activated antitumor drug release combined with the local hyperthermic treatment of cancer. 

Veronese FM, Schiavon O, Pasut G, Mendichi R, Andersson L, Tsirk A, Ford J, Wu G, Kneller S, Davies J, Duncan R (2005) PEG-doxorubicin conjugates influence of polymer structure on drug release, in vitro cytotoxicity, biodistribution, and antitumor activity. Bioconjug Chem 16 775-784... 

Fig. 4 A second generation of the drug loading micelle with a pH-sensitive drug releasing property, a Formation of pH-sensitive polymeric micelles from PEG-(PAsp-Hyd-Dox) block copolymers. Antitumor drugs (Dox), conjugated through acid-labile hydrazone linkers, are released in lower pH conditions, b Time- and pH-dependent Dox release profile from the micelles. The micelles selectively release Dox under the pH condition of region B, which corresponds to the intracellular environment. The amount of loaded Dox in the micelles was calculated from the released Dox at pH 3.0 where all of the loaded drugs were assumed to be released from the micelle...

Ionic rednction nsing a hydride occurs in vivo during the rednction catalyzed by NADH or NADPH enzymes, whereas one-electron rednction releases a radical structure, which may contribute to the toxic effect. Figure 33.13 illustrates the biotransformations affecting the anthracycline antitumor drug daunomycin. Recent stndies snggest that nitric oxide synthases may contribnte to the cardiotoxicity, probably becanse of their strnctnral similarities with CYP rednctase. ... 

An improvement of medical devices based on bacterial polymers by the encapsulation of different drugs, opens up the wide prospects in applications for these new devices with pharmacological activity in medicine. PHB polymer was used as a drug delivery matrix for sustaining the release of various drugs such as dipyridamole [DP], indomethacin and antibiotics (rifampicin, metronidazole, ciprofloxacin, levofloxacin), anti-inflammatory drugs (flurbiprofen, dexamethasone, prednisolone), and antitumor drugs (paclitaxel) [132]. 

Bae Y, Nishiyama N, Fukushima S, Koyama H, Yasuhiro M, Kataoka K. Preparation and biological characterization of polymeric micelle drug carriers with intracellular pH-triggered drug release property Tumor permeability, controlled subcellular drug distribution, and enhanced in vivo antitumor efficacy. Bioconjugate Chem 2005 16 122-130. 

Kawaguchi, T. et al. Control of drug release with a combination of prodrug and polymer matrix antitumor activity and release profiles of 2 ,3 -Diacyl-5-fluoro-2 -deoxy-uridine from poly(3-hydroxybutyrate) microspheres. J. Pharmaceutical Sci. 1992, 87(6), 508-512. 

Bonartsev,A. P. etal. Sustained release of the antitumor drug paclitaxel from poly(3-hydroxybu1yrate)-based microspheres. Biochem. (Moscow) Suppl. Ser. B Biomed. I Chem. 2012, 6(1), 42-47. 

Also, strong interactions (complexation) between the drug and the surfactant have been found to strongly affect the drug release rate in microemulsion formulations. For example, Gasco et al. [19] studied the release of doxorubicin, a hydrophilic antitumor drug, from a W/O microemulsion formed by lecithin, water, hexanol, and ethyl oleate and observed a reservoir effect due to complexation between doxorubicin and lecithin. 

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