About: Polymer conjugates of the highly potent cytostatic drug 2-pyrrolinodoxorubicin

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Description	This paper describes the synthesis and biological evaluation of a conjugate of the highly cytotoxic drug 2-pyrrolinodoxorubicin (p-DOX) with an N-(2-hydroxypropyl)methacrylamide copolymer (PHPMA), utilizing the advantageous concept of polymer–drug conjugates. The hydrazone bond between the polymer and drug is susceptible to pH-controlled hydrolysis, enabling prolonged stability in circulation and fast p-DOX release under conditions mimicking the intracellular environment. The in vitro cytostatic activity of free p-DOX was in accordance with literature, whereas its PHPMA conjugate exhibited a 1.3- to 5-fold lower cytotoxicity, depending on the cancer cell line, when compared to the free p-DOX. On mice bearing T-cell EL4 lymphoma, no tumor suppression was observed from the free p-DOX at a subtoxic dose of 0.1 mg/kg, whereas the PHPMA/p-DOX conjugate significantly inhibited the initial tumor growth at approximately equitoxic doses of 0.4 and 0.8 mg p-DOX eq/kg. This paper describes the synthesis and biological evaluation of a conjugate of the highly cytotoxic drug 2-pyrrolinodoxorubicin (p-DOX) with an N-(2-hydroxypropyl)methacrylamide copolymer (PHPMA), utilizing the advantageous concept of polymer–drug conjugates. The hydrazone bond between the polymer and drug is susceptible to pH-controlled hydrolysis, enabling prolonged stability in circulation and fast p-DOX release under conditions mimicking the intracellular environment. The in vitro cytostatic activity of free p-DOX was in accordance with literature, whereas its PHPMA conjugate exhibited a 1.3- to 5-fold lower cytotoxicity, depending on the cancer cell line, when compared to the free p-DOX. On mice bearing T-cell EL4 lymphoma, no tumor suppression was observed from the free p-DOX at a subtoxic dose of 0.1 mg/kg, whereas the PHPMA/p-DOX conjugate significantly inhibited the initial tumor growth at approximately equitoxic doses of 0.4 and 0.8 mg p-DOX eq/kg. (en)
Title	Polymer conjugates of the highly potent cytostatic drug 2-pyrrolinodoxorubicin Polymer conjugates of the highly potent cytostatic drug 2-pyrrolinodoxorubicin (en)
skos:prefLabel	Polymer conjugates of the highly potent cytostatic drug 2-pyrrolinodoxorubicin Polymer conjugates of the highly potent cytostatic drug 2-pyrrolinodoxorubicin (en)
skos:notation	RIV/61389013:_____/11:00353988!RIV11-AV0-61389013
http://linked.open...avai/predkladatel	Ústav makromolekulární chemie AV ČR, v. v. i.
http://linked.open...avai/riv/aktivita	P Z
http://linked.open...avai/riv/aktivity	P(IAAX00500803), Z(AV0Z40500505), Z(AV0Z50200510)
http://linked.open...iv/cisloPeriodika	1-2
http://linked.open...vai/riv/dodaniDat	2011
http://linked.open...aciTvurceVysledku	Ulbrich, Karel Studenovský, Martin
http://linked.open.../riv/druhVysledku	J - Článek v odborném periodiku
http://linked.open...iv/duvernostUdaju	S - Úplné a pravdivé údaje nepodléhající ochraně podle zvláštních právních předpisů
http://linked.open...titaPredkladatele	Ústav makromolekulární chemie AV ČR, v. v. i.
http://linked.open...dnocenehoVysledku	221224
http://linked.open...ai/riv/idVysledku	RIV/61389013:_____/11:00353988
http://linked.open...riv/jazykVysledku	eng - angličtina
http://linked.open.../riv/klicovaSlova	polymer conjugates; tumor drug-delivery; pH-controlled release (en)
http://linked.open.../riv/klicoveSlovo	pH-controlled release polymer conjugates tumor drug-delivery
http://linked.open...odStatuVydavatele	NL - Nizozemsko
http://linked.open...ontrolniKodProRIV	[63685A90A0E7]
http://linked.open...i/riv/nazevZdroje	European Journal of Pharmaceutical Sciences
http://linked.open...in/vavai/riv/obor	CD
http://linked.open...ichTvurcuVysledku	2 (xsd:int)
http://linked.open...cetTvurcuVysledku	4 (xsd:int)
http://linked.open...vavai/riv/projekt	Multifunctional Polymer Systems with Cytostatic and Immunomobilizing Activities
http://linked.open...UplatneniVysledku	2011
http://linked.open...v/svazekPeriodika	42
http://linked.open...iv/tvurceVysledku	Ulbrich, Karel Říhová, Blanka Studenovský, Martin Ibrahimová, Markéta
http://linked.open...ain/vavai/riv/wos	000286708600019
http://linked.open...n/vavai/riv/zamer	Progresivní makromolekulární materiály a supramolekulární systémy: syntéza a studium vlastností, jevů a možností využití pro speciální aplikace a moderní technologie Microorganisms in Research and Biotechnology
issn	0928-0987
number of pages	8 (xsd:int)
is http://linked.open...avai/riv/vysledek of	Polymer conjugates of the highly potent cytostatic drug 2-pyrrolinodoxorubicin Polymer conjugates of the highly potent cytostatic drug 2-pyrrolinodoxorubicin

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