Polymer carriers
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In this review we summarize several synthetic approaches to the advanced synthesis of star-like polymer-based drug carriers. Moreover, their application as nanomedicines for therapy or the diagnosis of neoplastic diseases and their biodistribution are reviewed in detail. From a broad spectrum of star-like systems, we focus only on fully water-soluble systems, mainly based on poly(ethylene glycol) or N-(2-hydroxypropyl)methacrylamide polymer and copolymer arms and polyamidoamine dendrimers serving as the core of the star-like systems.
- MeSH
- lidé MeSH
- methakryláty aplikace a dávkování chemie metabolismus MeSH
- nosiče léků aplikace a dávkování chemie metabolismus MeSH
- polyethylenglykoly aplikace a dávkování metabolismus MeSH
- polymery aplikace a dávkování chemie metabolismus MeSH
- tkáňová distribuce účinky léků fyziologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
A novel actively targeted polymer carrier for anticancer drugs based on an N-(2-hydroxypropyl)methacrylamide copolymer (PHPMA) is proposed. An oligopeptide sequence GE7, attached to the polymer, is a specific ligand for the EGF receptor overexpressed on most tumor cells. Co-attachment of selected chemotherapeutics will therefore lead to formation of tumor-specific polymer therapeutics, further enhanced by the EPR effect. FACS measurements prove elevated binding activity of the fluorescently labeled PHPMA/GE7 conjugate in EGFR-rich cells (FaDu, MCF-7), compared to conjugates of scrambled peptides. Cell lines with low EGFR level (SW620, B16F10) bind the GE7 conjugate significantly less.
- MeSH
- erbB receptory metabolismus MeSH
- kyseliny polymethakrylové chemická syntéza chemie terapeutické užití MeSH
- lékové transportní systémy metody MeSH
- lidé MeSH
- nádorové buněčné linie MeSH
- oligopeptidy genetika metabolismus MeSH
- pozitronová emisní tomografie MeSH
- protinádorové látky chemie metabolismus MeSH
- průtoková cytometrie MeSH
- spektrofotometrie ultrafialová MeSH
- spektrometrie hmotnostní - ionizace laserem za účasti matrice MeSH
- vysokoúčinná kapalinová chromatografie MeSH
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- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
Biocompatible polymers derived from ? -hydroxyacids, in particular homopolymers and copolymers of lactic and glycolic acids, are widely used in surgery, tissue engineering and drug formulation. Their polycondensation with polyhydric alcohols yields degradable low-molecularweight branched oligoesters. Polymer plasticizers improve processibility, decrease brittleness and impart mechanical endurance to the oligoesters. Out of many plasticizers used in polymers, only a few of them have been approved for pharmaceutical applications. The type and amount of plasticizers influence the degradation time of polymers and thus the drug release. Biodegradable polyesters are currently used in parenteral drug delivery as solid implants, microparticles and in-situ implants. Homopolymers and copolymers of lactic and glycolic acids are suitable drug carriers for the purpose in treatment of cancer, drug addiction, contraception and vaccination as well as for the controlled release of growth factors in tissue engineering.
In this work, design and synthesis of high-molecular-weight N-(2-hydroxypropyl)methacrylamide-based polymer drug delivery systems tailored for cancer therapy is summarized. Moreover, the influence of their architecture on tumor accumulation and in vivo anti-cancer efficacy is discussed. Mainly, the high-molecular-weight delivery systems, such as branched, grafted, multi-block, star-like or micellar systems, with molecular weights greater than the renal threshold are discussed and reviewed in detail.
We developed a new simplified method for the synthesis of well-defined linear, diblock, or starlike N-(2-hydroxypropyl)methacrylamide (HPMA)-based polymer drug carriers using controlled reversible addition-fragmentation chain transfer polymerization. The prepared monodispersed polymers are after the drug attachment intended for enhanced anticancer therapy. This new approach significantly reduces the number of required synthetic steps and minimizes the consumption of organic solvents during the synthesis. As a result, highly defined linear, diblock, and starlike copolymers designed for pH-triggered drug activation/release in tumor tissue were formed in sufficient amounts for further physicochemical and biological studies. Within the synthesis, we also developed a new procedure for the selective deprotection of tert-butoxycarbonyl hydrazide and amine groups on hydrophilic HPMA copolymers, including the one-pot removal of polymer end groups. We studied and described in detail the kinetics and efficacy of the deprotection reaction. We believe the simplified synthetic approach facilitates the preparation of polymer conjugates bound by the pH-sensitive hydrazone bond and their application in tumor treatment.
A simple molecular modeling method for the characterization of polymeric drug carriers is presented. Six biodegradable polymers have been investigated as drug carriers using molecular simulations: l-polylactide, d-polylactide, chitosan, polyglycolic acid, polyethylene glycol and cellulose. Cyclosporine A has been chosen as a model drug substance. Classical molecular dynamics and docking calculations were employed to model and predict polymer-drug interactions. These interactions have been analyzed by non-bond interaction energy and interaction parameter calculated using Flory-Huggins theory. Flexibility of polymer chains has been characterized by the change of gyration radius along the molecular dynamics trajectory. The relationship between mixing energy, chain length and chain flexibility has been revealed for each polymer/drug system.
- MeSH
- cyklosporin chemie MeSH
- molekulární modely * MeSH
- nosiče léků chemie MeSH
- polymery chemie MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
The enzymatic release of a model drug from a polymer carrier inside a tumor using multispectral optical imaging in vivo in nude mice bearing colorectal carcinomas HT-29 and DLD-1 is demonstrated. Much higher release rate in vivo from a linear (30 kDa) (N-2-hydroxypropyl)methacrylamide-based polymer compared with a high molecular weight branched (170 kDa) polymer conjugate is observed, probably due to steric hindrance of the cleavable spacer of the latter polymer to proteolytic enzymes. There is no significant difference in the relative biodistribution of the two polymers, but the branched polymer circulates much longer. Both polymers are labeled with two different fluorophores. Dyomics-676 as a drug model is attached to the polymer via an enzymatically cleavable Gly-Phe-Leu-Gly spacer; Dyomics 782 is bound to the same polymer via a nondegradable amide bond, enabling the tracking of the polymer carrier after i.v. application to mice.
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- akrylamidy * chemie farmakokinetika farmakologie MeSH
- fluorescenční barviva * chemie farmakokinetika farmakologie MeSH
- kolorektální nádory * farmakoterapie metabolismus patologie MeSH
- lidé MeSH
- myši nahé MeSH
- myši MeSH
- nosiče léků * chemie farmakokinetika farmakologie MeSH
- xenogenní modely - testy protinádorové aktivity MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
