Although several nanomedicines got clinical approval over the past two decades, the clinical translation rate is relatively small so far. There are many post-surveillance withdrawals of nanomedicines caused by various safety issues. For successful clinical advancement of nanotechnology, it is of unmet need to realize cellular and molecular foundation of nanotoxicity. Current data suggest that lysosomal dysfunction caused by nanoparticles is emerging as the most common intracellular trigger of nanotoxicity. This review analyzes prospect mechanisms of lysosomal dysfunction-mediated toxicity induced by nanoparticles. We summarized and critically assessed adverse drug reactions of current clinically approved nanomedicines. Importantly, we show that physicochemical properties have great impact on nanoparticles interaction with cells, excretion route and kinetics, and subsequently on toxicity. We analyzed literature on adverse reactions of current nanomedicines and hypothesized that adverse reactions might be linked with lysosomal dysfunction caused by nanomedicines. Finally, from our analysis it becomes clear that it is unjustifiable to generalize safety and toxicity of nanoparticles, since different particles possess distinct toxicological properties. We propose that the biological mechanism of the disease progression and treatment should be central in the optimization of nanoparticle design.
- MeSH
- lidé MeSH
- lyzozomy MeSH
- nanočástice * toxicita chemie MeSH
- nanomedicína * metody MeSH
- nanotechnologie metody MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
Layered double hydroxides (LDHs) are appealing nanomaterials for (bio)medical applications and their potential is threefold. One can gain advantage of the structure of LDH frame (i.e., layered morphology), anion exchanging property towards drugs with acidic character and tendency for facile surface modification with biopolymers. This review focuses on the third aspect, as it is necessary to evaluate the advantages of polymer adsorption on LDH surfaces. Beside the short discussion on fundamental and structural features of LDHs, LDH-biopolymer interactions will be classified in terms of the effect on the colloidal stability of the dispersions. Thereafter, an overview on the biocompatibility and biomedical applications of LDH-biopolymer composite materials will be given. Finally, the advances made in the field will be summarized and future research directions will be suggested.
- MeSH
- adsorpce MeSH
- biopolymery MeSH
- hydroxidy * chemie MeSH
- lidé MeSH
- nanočástice * chemie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Immune cells have emerged as powerful regulators of regenerative as well as pathological processes. The vast majority of regenerative immunoengineering efforts have focused on macrophages; however, growing evidence suggests that other cells of both the innate and adaptive immune system are as important for successful revascularization and tissue repair. Moreover, spatiotemporal regulation of immune cells and their signaling have a significant impact on the regeneration speed and the extent of functional recovery. In this review, we summarize the contribution of different types of immune cells to the healing process and discuss ways to manipulate and control immune cells in favor of vascularization and tissue regeneration. In addition to cell delivery and cell-free therapies using extracellular vesicles, we discuss in situ strategies and engineering approaches to attract specific types of immune cells and modulate their phenotypes. This field is making advances to uncover the extraordinary potential of immune cells and their secretome in the regulation of vascularization and tissue remodeling. Understanding the principles of immunoregulation will help us design advanced immunoengineering platforms to harness their power for tissue regeneration.
- MeSH
- biokompatibilní materiály MeSH
- hojení ran * MeSH
- imunita MeSH
- lidé MeSH
- makrofágy * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Research Support, N.I.H., Extramural MeSH
Therapeutic enzymes are valuable biopharmaceuticals in various biomedical applications. They have been successfully applied for fibrinolysis, cancer treatment, enzyme replacement therapies, and the treatment of rare diseases. Still, there is a permanent demand to find new or better therapeutic enzymes, which would be sufficiently soluble, stable, and active to meet specific medical needs. Here, we highlight the benefits of coupling computational approaches with high-throughput experimental technologies, which significantly accelerate the identification and engineering of catalytic therapeutic agents. New enzymes can be identified in genomic and metagenomic databases, which grow thanks to next-generation sequencing technologies exponentially. Computational design and machine learning methods are being developed to improve catalytically potent enzymes and predict their properties to guide the selection of target enzymes. High-throughput experimental pipelines, increasingly relying on microfluidics, ensure functional screening and biochemical characterization of target enzymes to reach efficient therapeutic enzymes.
Although oral drug delivery is the preferred administration route and has been used for centuries, modern drug discovery and development pipelines challenge conventional formulation approaches and highlight the insufficient mechanistic understanding of processes critical to oral drug absorption. This review presents the opinion of UNGAP scientists on four key themes across the oral absorption landscape: (1) specific patient populations, (2) regional differences in the gastrointestinal tract, (3) advanced formulations and (4) food-drug interactions. The differences of oral absorption in pediatric and geriatric populations, the specific issues in colonic absorption, the formulation approaches for poorly water-soluble (small molecules) and poorly permeable (peptides, RNA etc.) drugs, as well as the vast realm of food effects, are some of the topics discussed in detail. The identified controversies and gaps in the current understanding of gastrointestinal absorption-related processes are used to create a roadmap for the future of oral drug absorption research.
- MeSH
- aplikace orální MeSH
- gastrointestinální trakt metabolismus MeSH
- interakce mezi potravou a léky MeSH
- intestinální absorpce * MeSH
- léčivé přípravky chemie metabolismus MeSH
- lidé MeSH
- počítačová simulace MeSH
- příprava léků MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- MeSH
- akrylamidy * dějiny MeSH
- antitumorózní látky MeSH
- chemie farmaceutická * dějiny MeSH
- dějiny 20. století MeSH
- dějiny 21. století MeSH
- Check Tag
- dějiny 20. století MeSH
- dějiny 21. století MeSH
- Publikační typ
- biografie MeSH
- historické články MeSH
- oslavné články MeSH
- Geografické názvy
- Česká republika MeSH
- O autorovi
- Kopeček, Jindřich, 1940- Autorita
HPMA copolymers are one of the most promising drug carriers as their biophysical and biochemical properties, including their immunocompatibility, are very favorable. So far, there is no evidence that HPMA copolymers can interact with the immune system in a way that would lead either to suppression of some of its crucial functions or to inappropriate activation with possible serious side-effects and thus we can conclude that HPMA copolymers are convincingly proved to be "immunologically" safe. Moreover, it was shown both in mice and humans that HPMA copolymer-bound doxorubicin (DOX-HPMA) conjugates possess besides powerful anti-tumor effect also various immunomodulatory properties and exert significantly decreased side-toxicities, minimized bone marrow toxicity and cardiotoxicity being the most important ones. The possibility to induce potent and long-lasting tumor-specific immunity during the treatment with these compounds which is capable to provide protection against minimal residual disease is one of the most important and therapeutically valuable features of these conjugates.
- MeSH
- akrylamidy chemie imunologie terapeutické užití MeSH
- antitumorózní látky chemie terapeutické užití MeSH
- chemorezistence imunologie MeSH
- imunologické faktory chemie imunologie terapeutické užití MeSH
- lidé MeSH
- nádory farmakoterapie imunologie MeSH
- polymery chemie terapeutické užití MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
Synthetic strategies and chemical and structural aspects of the synthesis of HPMA copolymer conjugates with various drugs and other biologically active molecules are described and discussed in this chapter. The discussion is held from the viewpoint of design and structure of the polymer backbone and biodegradable spacer between a polymer and drug, structure and methods of attachment of the employed drugs to the carrier and structure and methods of conjugation with targeting moieties. Physicochemical properties of the water-soluble polymer-drug conjugates and polymer micelles including mechanisms of drug release are also discussed. Detailed description of biological behavior of the polymer-drug conjugates as well as application of the copolymers for surface modification and targeting of gene delivery vectors are not included, they are presented and discussed in separate chapters of this issue.
- MeSH
- akrylamidy aplikace a dávkování chemie MeSH
- lidé MeSH
- molekulární struktura MeSH
- nosiče léků aplikace a dávkování chemie MeSH
- polymery aplikace a dávkování chemie MeSH
- systémy cílené aplikace léků metody MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
This paper reviews an early clinical experience with anthracycline (epirubicin; Epi or doxorubicin; Dox) containing an N-(2-hydroyxypropyl)methacrylamide copolymer carrier targeted with autologous or commercial human immunoglobulin in six patients aged 28-55 suffering from therapy-resistant metastatic cancer. More than 100 biochemical, hematological and immunological parameters, including nine tumor markers, were tested in blood samples taken 24 h after the first and up to 10 months after the last application. The intravenous application proceeded without serious adverse or side effects and did not require hospitalization. Cardiotoxicity was not observed. Four of six monitored patients attained stabilization of disease (liver ultrasound scan and bone computer tomography) with a very good quality of life lasting from seven up to 18 months. Positive response to the treatment was, among others, evaluated as decreased CA 15-3 and CEA tumor markers. In three of five tested patients the serum level of C-reactive protein was temporarily increased 72 h after the treatment. A stable or elevated number of peripheral blood reticulocytes together with activation of natural killer (NK) cells and lymphokine-activated killer (LAK) cells supports the data previously obtained in experimental animals pointing to a dual role, i.e. the cytotoxic and immunomobilizing character of doxorubicin-HPMA conjugates.
- MeSH
- akrylamidy MeSH
- antibiotika antitumorózní aplikace a dávkování škodlivé účinky terapeutické užití MeSH
- chemorezistence MeSH
- dospělí MeSH
- doxorubicin analogy a deriváty aplikace a dávkování škodlivé účinky terapeutické užití MeSH
- epirubicin aplikace a dávkování škodlivé účinky terapeutické užití MeSH
- hemangiosarkom farmakoterapie MeSH
- imunoglobulin G aplikace a dávkování imunologie MeSH
- imunologické faktory aplikace a dávkování imunologie MeSH
- intravenózní imunoglobuliny aplikace a dávkování imunologie MeSH
- kvalita života MeSH
- kyseliny polymethakrylové aplikace a dávkování škodlivé účinky terapeutické užití MeSH
- lidé středního věku MeSH
- lidé MeSH
- metastázy nádorů MeSH
- nádorové biomarkery krev MeSH
- nádory prsu farmakoterapie MeSH
- nosiče léků chemie MeSH
- systémy cílené aplikace léků MeSH
- výsledek terapie MeSH
- zvířata MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- práce podpořená grantem MeSH
- MeSH
- adjuvancia imunologická aplikace a dávkování farmakologie MeSH
- antitumorózní látky aplikace a dávkování farmakologie MeSH
- doxorubicin aplikace a dávkování farmakologie MeSH
- finanční podpora výzkumu jako téma MeSH
- lidé MeSH
- polymery farmakologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
