Recently, numerous polymer materials have been employed as drug carrier systems in medicinal research, and their detailed properties have been thoroughly evaluated. Water-soluble polymer carriers play a significant role between these studied polymer systems as they are advantageously applied as carriers of low-molecular-weight drugs and compounds, e.g., cytostatic agents, anti-inflammatory drugs, antimicrobial molecules, or multidrug resistance inhibitors. Covalent attachment of carried molecules using a biodegradable spacer is strongly preferred, as such design ensures the controlled release of the drug in the place of a desired pharmacological effect in a reasonable time-dependent manner. Importantly, the synthetic polymer biomaterials based on N-(2-hydroxypropyl) methacrylamide (HPMA) copolymers are recognized drug carriers with unique properties that nominate them among the most serious nanomedicines candidates for human clinical trials. This review focuses on advances in the development of HPMA copolymer-based nanomedicines within the passive and active targeting into the place of desired pharmacological effect, tumors, inflammation or bacterial infection sites. Specifically, this review highlights the safety issues of HPMA polymer-based drug carriers concerning the structure of nanomedicines. The main impact consists of the improvement of targeting ability, especially concerning the enhanced and permeability retention (EPR) effect.

• Klíčová slova
• EPR effect, HPMA copolymers, controlled release, drug delivery, nanomedicines,
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Doxorubicin-conjugated magnetic nanoparticles containing hydrolyzable hydrazone bonds were developed using a non-toxic poly[N-(2-hydroxypropyl)methacrylamide] (PHPMA) coating, which ensured good colloidal stability in aqueous media and limited internalization by the cells, however, enabled adhesion to the cell surface. While the neat PHPMA-coated particles proved to be non-toxic, doxorubicin-conjugated particles exhibited enhanced cytotoxicity in both drug-sensitive and drug-resistant tumor cells compared to free doxorubicin. The newly developed doxorubicin-conjugated PHPMA-coated magnetic particles seem to be a promising magnetically targeted vehicle for anticancer drug delivery.

• Klíčová slova
• cytotoxicity, doxorubicin, magnetic, nanoparticles, poly[N-(2-hydroxypropyl)methacrylamide],
• Publikační typ
• časopisecké články MeSH

Drug targeting is an attractive new approach to killing cancer cells while leaving normal tissue unharmed. Recently we have developed a new generation of antibody-targeted immunosuppressive (cyclosporin A) and cytostatic (daunomycin, doxorubicin) drugs and photosensitizers (chlorin e6) effective in vitro and in vivo. The drugs and the targeting antibody (polyclonal and monoclonal) are conjugated to the oligopeptidic side chains of a water-soluble synthetic carrier, copolymer of N-(2-hydroxypropyl)methacrylamide. The composition of the side chains ensures the stability of the linkage between the drug and the polymeric carrier in the bloodstream and its intralysosomal degradability which is a prerequisite for the pharmacological activity of the preparation. Antibody-targeted polymer bound drugs show considerably decreased hepatotoxicity, cardiotoxicity, myelotoxicity and nephrotoxicity. Two adriamycin-HPMA copolymers are in Phase I/II clinical trials in United Kingdom.

• MeSH
• akrylamidy aplikace a dávkování   škodlivé účinky   chemie   farmakokinetika   MeSH
• antigeny Thy-1 imunologie   MeSH
• chlorofylidy MeSH
• cyklosporin aplikace a dávkování   škodlivé účinky   farmakokinetika   MeSH
• daunomycin terapeutické užití   MeSH
• doxorubicin analogy a deriváty   terapeutické užití   MeSH
• imunokonjugáty * aplikace a dávkování   škodlivé účinky   chemie   farmakokinetika   MeSH
• imunosupresiva aplikace a dávkování   škodlivé účinky   chemie   farmakokinetika   MeSH
• klinické zkoušky jako téma MeSH
• kyseliny polymethakrylové terapeutické užití   MeSH
• lidé MeSH
• lyzozomy metabolismus   MeSH
• MHC antigeny II. třídy imunologie   MeSH
• monoklonální protilátky aplikace a dávkování   chemie   imunologie   farmakokinetika   MeSH
• myši inbrední BALB C MeSH
• myši nahé MeSH
• myši MeSH
• nádory farmakoterapie   MeSH
• nemoci imunitního systému farmakoterapie   MeSH
• porfyriny aplikace a dávkování   škodlivé účinky   farmakokinetika   MeSH
• protinádorová antibiotika aplikace a dávkování   škodlivé účinky   farmakokinetika   MeSH
• protinádorové látky aplikace a dávkování   škodlivé účinky   farmakokinetika   MeSH
• radiosenzibilizující látky aplikace a dávkování   škodlivé účinky   chemie   farmakokinetika   MeSH
• T-lymfocyty - podskupiny imunologie   MeSH
• tkáňová distribuce MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• akrylamidy MeSH
• antigeny Thy-1 MeSH
• chlorofylidy MeSH
• cyklosporin MeSH
• daunomycin-N-(2-hydroxypropyl)methacrylamide copolymer conjugate MeSH Prohlížeč
• daunomycin MeSH
• doxorubicin-N-(2-hydroxypropyl)methacrylamide copolymer conjugate MeSH Prohlížeč
• doxorubicin MeSH
• imunokonjugáty * MeSH
• imunosupresiva MeSH
• kyseliny polymethakrylové MeSH
• MHC antigeny II. třídy MeSH
• monoklonální protilátky MeSH
• N-(2-hydroxypropyl)methacrylamide MeSH Prohlížeč
• phytochlorin MeSH Prohlížeč
• porfyriny MeSH
• protinádorová antibiotika MeSH
• protinádorové látky MeSH
• radiosenzibilizující látky MeSH