Cíl: Studie se zabývá lingvistickou validací a vybranými aspekty (konstruktové validity a reliability) dotazníku hodnocení inzulinového aplikačního systému (IDSRQ). Metodika: Zkoumaný soubor tvořilo 151 pacientů s diabetem mellitem 1. typu. Byla provedena jazyková a obsahová validace IDSRQ. Výsledky dotazníku a jednotlivých subškál byly zpracovány pomocí deskriptivní statistiky a faktorové analýzy. Výsledky: Data byla použita k výpočtu reliability sedmi původních subškál (0,42–0,92). Platnost konstruktu byla testována pomocí explorační a konfirmační faktorové analýzy. Byly vytvořeny modely M1, M2 a M3. Pro modely M2 a M3 byla vypočtena významnost chí-kvadrát testu (p < 0,001) a FIT indexů. Jako nejlepší byl označen pětifaktorový model se spolehlivostí 0,69–0,89 v subškálách. Závěr: Nová verze dotazníku je v souladu s psychometrickými vlastnostmi původního nástroje a extrakce položek do pětifaktorového řešení odráží aktuální hodnocení spokojenosti pacientů s léčbou diabetu mellitu 1. typu v českém prostředí.
Aim: The study deals with the linguistic validation and selected aspects (constructive validity and reliability) of the Insulin Delivery System Rating Questionnaire (IDSRQ). Methods: The examined file consisted of 151 patients with type 1 diabetes mellitus. The linguistic and content validation IDSRQ was performed, and the results of the questionnaire and individual subscales were processed via descriptive statistics and factor analysis. Results: The data was used to calculate the reliability of seven original subscales (0.42-0.92). Construct validity was tested via exploratory and confirmatory factor analysis. Models M1, M2 and M3, were created. For models M2 and M3, the significance of the chi-square test (p < 0.001) and FIT indices was calculated. The five-factor model with a reliability of 0.69-0.89 in subscales was identified as the best. Conclusion: The new version of the questionnaire is in line with the psychometric properties of the original tool, and the extraction of items into a five-factor solution reflects the current assessment of patients' satisfaction with type 1 diabetes mellitus therapy in the Czech environment.
Effective drug delivery is restricted by pathophysiological barriers in solid tumors. In human pancreatic adenocarcinoma, poorly-permeable blood vessels limit the intratumoral permeation and penetration of chemo or nanotherapeutic drugs. New and clinically viable strategies are urgently sought to breach the neoplastic barriers that prevent effective drug delivery. Here, we present an original idea to boost drug delivery by selectively knocking down the tumor vascular barrier in a human pancreatic cancer model. Clinical radiation activates the tumor endothelial-targeted gold nanoparticles to induce a physical vascular damage due to the high photoelectric interactions. Active modulation of these tumor neovessels lead to distinct changes in tumor vascular permeability. Noninvasive MRI and fluorescence studies, using a short-circulating nanocarrier with MR-sensitive gadolinium and a long-circulating nanocarrier with fluorescence-sensitive nearinfrared dye, demonstrate more than two-fold increase in nanodrug delivery, post tumor vascular modulation. Functional changes in altered tumor blood vessels and its downstream parameters, particularly, changes in Ktrans (permeability), Kep (flux rate), and Ve (extracellular interstitial volume), reflect changes that relate to augmented drug delivery. The proposed dual-targeted therapy effectively invades the tumor vascular barrier and improve nanodrug delivery in a human pancreatic tumor model and it may also be applied to other nonresectable, intransigent tumors that barely respond to standard drug therapies.
- MeSH
- Human Umbilical Vein Endothelial Cells metabolism MeSH
- Neoplasms, Experimental * blood supply diagnostic imaging drug therapy metabolism MeSH
- Metal Nanoparticles * chemistry therapeutic use MeSH
- Drug Delivery Systems * MeSH
- Humans MeSH
- Magnetic Resonance Angiography * MeSH
- Mice MeSH
- Cell Line, Tumor MeSH
- Optical Imaging * MeSH
- Neovascularization, Pathologic * diagnostic imaging drug therapy metabolism MeSH
- Gold * chemistry pharmacokinetics pharmacology MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
- Publication type
- Journal Article MeSH
- Published Erratum MeSH
High-molecular-weight star polymer drug nanocarriers intended for the treatment and/or visualisation of solid tumours were synthesised, and their physico-chemical and preliminary in vitro biological properties were determined. The water-soluble star polymer carriers were prepared by the grafting of poly(amido amine) (PAMAM) dendrimers by hetero-telechelic N-(2-hydroxypropyl)methacrylamide (HPMA) copolymers, synthesised by the controlled radical Reversible Addition Fragmentation chain Transfer (RAFT) polymerisation. The well-defined star copolymers with Mw values ranging from 2 · 10(5) to 6 · 10(5) showing a low dispersity (approximately 1.2) were prepared in a high yield. A model anticancer drug, doxorubicin, was bound to the star polymer through a hydrazone bond, enabling the pH-controlled drug release in the target tumour tissue. The activated polymer arm ends of the star copolymer carrier enable a one-point attachment for the targeting ligands and/or a labelling moiety. In this study, the model TAMRA fluorescent dye was used to prove the feasibility of the polymer carrier visualisation by optical imaging in vitro. The tailor-made structure of the star polymer carriers should facilitate the synthesis of targeted polymer-drug conjugates, even polymer theranostics, for simultaneous tumour drug delivery and imaging.
- MeSH
- Dendrimers * chemical synthesis chemistry pharmacokinetics pharmacology MeSH
- Doxorubicin * chemistry pharmacokinetics pharmacology MeSH
- Delayed-Action Preparations chemical synthesis chemistry pharmacokinetics pharmacology MeSH
- Humans MeSH
- Methacrylates * chemistry pharmacokinetics pharmacology MeSH
- Mice MeSH
- Cell Line, Tumor MeSH
- Neoplasms * drug therapy metabolism pathology MeSH
- Nanoparticles chemistry ultrastructure MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
... Plan of action 36 -- 8.1 Guidelines for international action to promote integrated health care delivery ... ... Building physical capacity 41 -- 8.3.4 Networking 41 -- Acknowledgements 43 -- References 44 -- Selected ...
WHO technical report series ; 861
V, 68 s. : obr., tab. ; 23 cm
- MeSH
- Delivery of Health Care MeSH
- Primary Health Care MeSH
- Community Health Services organization & administration MeSH
- Conspectus
- Veřejné zdraví a hygiena
- NML Fields
- veřejné zdravotnictví
- management, organizace a řízení zdravotnictví
- NML Publication type
- publikace WHO
The focus of this review is to describe the state-of-art in the development of innovative drug delivery systems for phthalocyanines as photosensitizers for photodynamic therapy (PDT). PDT is a medical treatment combining photosensitizers (PSs) activated by visible light of a specific wavelength to selectively destroy targeted cells, tumor tissues and its surrounding vasculature. In the last decades, PDT has been under intense investigation, first as a promising alternative approach for improved cancer treatment, later against microbial infection and nowadays, mainly in aesthetic medicine, against age-related degeneration. The success of PDT is restricted because of difficulties with administration and skin permeation of PSs. As PDT importance raises, there is high interest for advanced formulations and delivery systems (DDS) for PS, especially formulations based on nanotechnology. Accordingly, this review deals with the innovations pertaining to DDS for PDT as disclosed in recent patents and literature.
- MeSH
- Photochemotherapy * MeSH
- Photosensitizing Agents administration & dosage MeSH
- Indoles administration & dosage MeSH
- Drug Delivery Systems * MeSH
- Humans MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Systematic Review MeSH
Up to now the lipid bilayers were rarely considered as targets in cancer therapy despite pronounced differences in lipid composition between plasma membranes of benign and malignant cells. In this study we demonstrate that the lipid bilayer of the plasma membrane is druggable and suitable for facilitating selective delivery of amphiphilic gemcitabine-squalene nanomedicines to cancer cells. Data from radioactive assays, fluorescent membrane probes and molecular dynamics simulations provide evidence of selective accumulation of gemcitabine-squalene in the plasma membranes with disrupted lipid asymmetry and its subsequent preferential uptake by malignant cells. This causes pronounced cytotoxicity on cancer cells in comparison to their benign counterparts originating from the same tissue.
- MeSH
- Cell Membrane metabolism MeSH
- Gemcitabine MeSH
- Lipid Bilayers metabolism MeSH
- Neoplasms * metabolism MeSH
- Prodrugs * MeSH
- Squalene metabolism MeSH
- Publication type
- Journal Article MeSH
Advanced drug delivery micro- and nanosystems have been widely explored due to their appealing specificity/selectivity, biodegradability, biocompatibility, and low toxicity. They can be applied for the targeted delivery of pharmaceuticals, with the benefits of good biocompatibility/stability, non-immunogenicity, large surface area, high drug loading capacity, and low leakage of drugs. Cardiovascular diseases, as one of the primary mortalities cause worldwide with significant impacts on the quality of patients' life, comprise a variety of heart and circulatory system pathologies, such as peripheral vascular diseases, myocardial infarction, heart failure, and coronary artery diseases. Designing novel micro- and nanosystems with suitable targeting properties and smart release behaviors can help circumvent crucial challenges of the tolerability, low stability, high toxicity, and possible side- and off-target effects of conventional drug delivery routes. To overcome different challenging issues, namely physiological barriers, low efficiency of drugs, and possible adverse side effects, various biomaterials-mediated drug delivery systems have been formulated with reduced toxicity, improved pharmacokinetics, high bioavailability, sustained release behavior, and enhanced therapeutic efficacy for targeted therapy of cardiovascular diseases. Despite the existing drug delivery systems encompassing a variety of biomaterials for treating cardiovascular diseases, the number of formulations currently approved for clinical use is limited due to the regulatory and experimental obstacles. Herein, the most recent advancements in drug delivery micro- and nanosystems designed from different biomaterials for the treatment of cardiovascular diseases are deliberated, with a focus on the important challenges and future perspectives.
- MeSH
- Biocompatible Materials MeSH
- Cardiovascular Diseases * drug therapy MeSH
- Drug Delivery Systems MeSH
- Delayed-Action Preparations MeSH
- Humans MeSH
- Drug Compounding MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
Silymarin is a well-known standardized extract from the seeds of milk thistle (Silybum marianum L., Asteraceae) with a pleiotropic effect on human health, including skin anticancer potential. Detailed characterization of flavonolignans properties affecting interactions with human skin was of interest. The partition coefficients log Pow of main constitutive flavonolignans, taxifolin and their respective dehydro derivatives were determined by a High Performance Liquid Chromatography (HPLC) method and by mathematical (in silico) approaches in n-octanol/water and model lipid membranes. These parameters were compared with human skin intake ex vivo. The experimental log Pow values for individual diastereomers were estimated for the first time. The replacement of n-octanol with model lipid membranes in the theoretical lipophilicity estimation improved the prediction strength. During transdermal transport, all the studied compounds permeated the human skin ex vivo; none of them reached the acceptor liquid. Both experimental/theoretical tools allowed the studied polyphenols to be divided into two groups: low (taxifolin, silychristin, silydianin) vs. high (silybin, dehydrosilybin, isosilybin) lipophilicity and skin intake. In silico predictions can be usefully applied for estimating general lipophilicity trends, such as skin penetration or accumulation predictions. However, the theoretical models cannot yet provide the dermal delivery differences of compounds with very similar physico-chemical properties; e.g., between diastereomers.
- MeSH
- Hydrophobic and Hydrophilic Interactions MeSH
- Drug Delivery Systems * MeSH
- Humans MeSH
- Silybum marianum chemistry MeSH
- Permeability MeSH
- Polyphenols administration & dosage chemistry pharmacology MeSH
- Dermis drug effects MeSH
- Thermodynamics MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
