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

Targeted drug delivery using nano-sized carrier systems with targeting functions to malignant and inflammatory tissue and tailored controlled drug release inside targeted tissues or cells has been and is still intensively studied. A detailed understanding of the correlation between the pharmacokinetic properties and structure of the nano-sized carrier is crucial for the successful transition of targeted drug delivery nanomedicines into clinical practice. In preclinical research in particular, fluorescence imaging has become one of the most commonly used powerful imaging tools. Increasing numbers of suitable fluorescent dyes that are excitable in the visible to near-infrared (NIR) wavelengths of the spectrum and the non-invasive nature of the method have significantly expanded the applicability of fluorescence imaging. This chapter summarizes non-invasive fluorescence-based imaging methods and discusses their potential advantages and limitations in the field of drug delivery, especially in anticancer therapy. This chapter focuses on fluorescent imaging from the cellular level up to the highly sophisticated three-dimensional imaging modality at a systemic level. Moreover, we describe the possibility for simultaneous treatment and imaging using fluorescence theranostics and the combination of different imaging techniques, e.g., fluorescence imaging with computed tomography.

• Klíčová slova
• drug delivery, fluorescence imaging, noninvasive imaging, polymers, theranostics,
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Here, we describe a novel polymer platform suitable for efficient diagnostics and potential theranostics based on 89Zr-labeled N-(2-hydroxypropyl)methacrylamide (HPMA)-based copolymer conjugates. A set of polymers differing in molecular weight with either low dispersity or high dispersity were designed and synthesized and their biodistribution in vivo was successfully and precisely observed over 72 h. Moreover, the feasibility of two imaging techniques, fluorescence imaging (FI) and positron emission tomography (PET), was compared using labeled polymer conjugates. Both methods gave comparable results thus showing the enhanced diagnostic potential of the prepared polymer-dye or polymer-chelator-89Zr constructs. The in vivo and ex vivo PET/FI studies indicated that the dispersity and molecular weight of the linear HPMA polymers have a significant influence on the pharmacokinetics of the polymer conjugates. The higher molecular weight and narrower distribution of molecular weights of the polymer carriers improve their pharmacokinetic profile for highly prolonged blood circulation and enhanced tumor uptake. Moreover, the same polymer carrier with the anticancer drug doxorubicin bound by a pH-sensitive hydrazone bond showed higher cytotoxicity and cellular uptake in vitro. Therefore, HPMA copolymers with low dispersity and a molecular weight near the limit of renal filtration can be used as highly efficient polymer carriers of tumor-targeted therapeutics or for theranostics with minimal side effects.

• MeSH
• doxorubicin aplikace a dávkování   farmakokinetika   MeSH
• experimentální nádory diagnostické zobrazování   farmakoterapie   MeSH
• Jurkat buňky MeSH
• lidé MeSH
• MFC-7 buňky MeSH
• myši inbrední BALB C MeSH
• myši MeSH
• nádorové buněčné linie MeSH
• nosiče léků chemie   MeSH
• optické zobrazování * MeSH
• polymery chemie   MeSH
• pozitronová emisní tomografie * MeSH
• radionuklidy MeSH
• teranostická nanomedicína * MeSH
• tkáňová distribuce MeSH
• zirkonium MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• doxorubicin MeSH
• nosiče léků MeSH
• polymery MeSH
• radionuklidy MeSH
• Zirconium-89 MeSH Prohlížeč
• zirkonium MeSH