Drugs doxorubicin

Fig. 10 Multifunctional solid biodegradable PLGA nanoparticles attached to several moieties such as T-cell antibodies, magnetic resonance contrast agent (biotin-BSA-Gd-DTPA) and encapsulated immunosuppressive drug (doxorubicin). (Adapted from [48])...

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). 

The polyketides are a large family of bio synthetically related NPs, some of which have very great pharmaceutical value (polyketide sales total about 10 billion annually, see also Chapter 7). Some antibiotics (erythromycin, monensin, rifamycin), immunosuppressants (rapamycin), antifungal substances (amphotericin), antiparasitic (aver-mectin) and anticancer drugs (doxorubicin) are polyketides. The term polyketide refers to the fact that the basic carbon skeleton is not a simple hydrocarbon chain as in the case of fatty acids but is a series of linked keto groups in sequence (Figure 3.6). The first phase of this pathway, the generation of carbon skeleton diversification. 

Reconstitution of full-length BRCAl into mouse embryonic fibroblast cells with a disrupted BRCAl led to an increase in resistance to several DNA damaging agents, including the platinum compounds carboplatin and oxaliplatin, the topoisomerase 1 drugs irinotecan and topotecan, and the topoisomerase 11 drugs doxorubicin and etoposide (61). 

The drugs doxorubicin and nitrofurantoin and the herbicide paraquat can acquire electrons from a source such as a reductase enzyme (Fig. 4.75). 

To increase the antiparasitic effect of methotrexate [254,255] and the more potent drugs doxorubicin [181] and muramyl dipeptide (MDP) [182], these drugs were coupled to manHSA. The beneficial effects of selective uptake of these drugs in KC was examined in mice infected with Leishmania parasites. These conjugates all inhibited the growth of these parasites in the macrophages predominantly in the liver but also in the spleen after repeated injections of the conjugate in leishmaniasis-infected mice. 

For example, surfaces comprising PNIPAM microgels were utilized for drug delivery [138], Electrostatic layer-by-layer assembly with poly(NIPAM-coacrylic acid) and poly(allylamine hydrochloride) on an amino-functionalized surface yielded thermoresponsive thin films. These were capable of a thermally regulated uptake and release of the chemotherapeutic drug doxorubicin. The films were loaded... 

ANALGESICS-celecoxib, opioids 2. ANTIARRHYTHMICS -amiodarone, flecainide, propafenone 3. ANTICANCER DRUGS - doxorubicin... 

SORAFENIB ANTICANCER AND IMMUNOMODULATING DRUGS-DOXORUBICIN Possible 1 doxorubicin levels Uncertain Watch for poor response to doxorubicin... 

Cardiotoxicity, which can lead to congestive heart failure and death, is a toxic effect of the anticancer drug, doxorubicin. A cumulative dose-effect analysis demonstrated that doxorubicin cardiotoxicity is related to the lifetime dose of the drug (Figure 18.12) and provided the basis for the definition of safe lifetime dose levels (7). The lifetime dose of doxorubicin is now limited to less than 400-450 mg/m, which is associated with a <5% risk of developing congestive heart failure. 

Prototype drug Doxorubicin (Adriamycin). Other examples in class daunorubicin, idarubicin, epirubicin, liposomal doxorubicin, liposomal daunorubicin. 

Cytotoxic antibiotics produce their effect mainly by direct action on DNA. Anthracyclines include the important drugs doxorubicin, aclarubicin and idarubicin. Related compounds are mitozantrone and epirubicin. Some others are the Streptomyces antibiotic dactinomycin. and the metalchelating glycopeptides especially bleomycins. Mitomycin effectively is a prodrug that is converted in the body to an alkylating agent. 

The following chapter introduces a remote loading procedure for anthracyclines focussing on the well-established drug doxorubicin. 

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