Fine tuning of the pH-dependent drug release rate from polyHPMA-ellipticinium conjugates.
Polymer conjugates of anticancer drugs have shown high potential for assisting in cancer treatments. The pH-labile spacers allow site-specific triggered release of the drugs. We synthesized and characterized model drug conjugates with hydrazide bond-containing poly[N-(2-hydroxypropyl)methacrylamide] differing in the chemical surrounding of the hydrazone bond-containing spacer to find structure-drug release rate relationships. The conjugate selected for further studies shows negligible drug release in a pH 7.4 buffer but released 50% of the ellipticinium drug within 24h in a pH 5.0 phosphate saline buffer. The ellipticinium drug retained the antiproliferative activity of the ellipticine.
Institute of Macromolecular Chemistry AS CR, Prague, Czech Republic.
Ondřej
O
Sedláček
Martin
M
Studenovský
David
D
Větvička
Karel
K
Ulbrich
Martin
M
Hrubý
D000178:Acrylamides / Q000737:chemistry*; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D004337:Drug Carriers / Q000138:chemical synthesis / Q000737:chemistry*; D004611:Ellipticines / Q000737:chemistry*; D006801:Humans; D006835:Hydrazones / Q000737:chemistry; D006863:Hydrogen-Ion Concentration
D000178:Acrylamides; D000970:Antineoplastic Agents; D004337:Drug Carriers; D004611:Ellipticines; D006835:Hydrazones; D004247:DNA; C032976:N-(2-hydroxypropyl)methacrylamide
Controlled release; Drug delivery; Ellipticine; Hydrazone; PolyHPMA