[Polymer and oligomer based doxorubicin carriers].
Doxorubicin and other anthracycline derivatives play an important role in the treatment of many malignant diseases. Unfortunately, clinical effectiveness of this class of drugs is limited by cumulative cardiotoxicity which occurs in significant percentage of patients at cumulative dose in the range 450-600 mg/m2. Therefore, several strategies have been developed to reduce cardiotoxicity of doxorubicin and its analogues. One of the possible ways leading to the improvement of anticancer selectivity of doxorubicin is the design of polymer and olygomer carriers which may transport drug molecules more efficiently and more specifically. Synthetic polymers are of increasing interest as therapeutic agents owing to their enhanced pharmacokinetic profiles relative to small molecule drugs. Currently a new class of multifunctional polymers is being prepared that can "mask" biologically active compounds, such as cytotoxic agents, until they reach target sites, but which can then release the agent in situ to effect the therapy. The legitimacy of the development of polymer based doxorubicine carriers is supported by the growing number of clinical reports indicating that the use of hydrophilic polymers or polymer coated liposomes as a platform for delivery of the drug results in better therapeutic effects than the free drug. In this article we present the most promising strategies directed at the development of improved anthracycline drugs formulations based of polymer and olygomer carriers. We review: 1) polyethylenoglycol-coated ("pegylated") liposomal doxorubicin; 2) extracellulary tumor-activated prodrugs which are conjugates of doxorubicin with peptides; 3) doxorubicin coated by higly polymerised glycosoaminoglycans; 4) conjugates of doxorubicin with copolymer of N-(2-hydroxypropyl)methacrylamide.
Kik
Krzysztof
K
Katedra Chemii Biomedycznej Zakład Farmakologii Molekularnej Uniwersytetu Medycznego w Łodzi. chemgen@csk.umed.lodz.pl
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Felicja
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Szmigiero
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D000178:Acrylamides / Q000737:chemistry / Q000493:pharmacokinetics; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage*; D004337:Drug Carriers; D006025:Glycosaminoglycans / Q000737:chemistry / Q000493:pharmacokinetics; D006801:Humans; D008081:Liposomes; D011092:Polyethylene Glycols / Q000737:chemistry / Q000493:pharmacokinetics; D011108:Polymers / Q000737:chemistry* / Q000493:pharmacokinetics*
D000178:Acrylamides; D000903:Antibiotics, Antineoplastic; D004337:Drug Carriers; D006025:Glycosaminoglycans; D008081:Liposomes; D011108:Polymers; D011092:Polyethylene Glycols; D004317:Doxorubicin; C032976:N-(2-hydroxypropyl)methacrylamide