Abstract:The clinical outcome of patients with ischemic heart disease can be significantly improved with the implementation of targeted drug delivery into the ischemic myocardium. In this paper, we present our original findings relevant to the problem of therapeutic heart targeting with use of nanoparticles. Experimental approaches included fabrication of carbon and silica nanoparticles, their characterization and surface modification. The acute hemodynamic effects of nanoparticle formulation as well as nanoparticle biodistribution were studied in male Wistar rats. Carbon and silica nanoparticles are nontoxic materials that can be used as carriers for heart-targeted drug delivery. Concepts of passive and active targeting can be applied to the development of targeted drug delivery to the ischemic myocardial cells. Provided that ischemic heart-targeted drug delivery can be proved to be safe and efficient, the results of this research may contribute to the development of new technologies in the pharmaceutical industry.
Abstract:The fluorophore indocyanine green accumulates in areas of ischemia-reperfusion injury due to an increase in vascular permeability and extravasation of the dye. The aim of the study was to validate an indocyanine green-based technique of in vivo visualization of myocardial infarction. A further aim was to quantify infarct size ex vivo and compare this technique with the standard triphenyltetrazolium chloride staining. Wistar rats were subjected to regional myocardial ischemia (30 minutes) followed by reperfusion (n = 7). Indocyanine green (0.25 mg/mL in 1 mL of normal saline) was infused intravenously for 10 minutes starting from the 25th minute of ischemia. Video registration in the near-infrared fluorescence was performed. Epicardial fluorescence of indocyanine green corresponded to the injured area after 30 minutes of reperfusion. Infarct size was similar when determined ex vivo using traditional triphenyltetrazolium chloride assay and indocyanine green fluorescent labeling. Intravital visualization of irreversible injury can be done directly by fluorescence on the surface of the heart. This technique may also be an alternative for ex vivo measurements of infarct size.
One of the disadvantages of photodynamic therapy is impossibility to specify the method according to biological features of malignant tumor such as a degree of blood supply, accumulation of photosensibilizator in tumorous tissue, proliferative activity and etc. The authors aimed to develop a mode of individualization of endobronchial photodynamic therapy of central non-small cell carcinoma of lung and assessment of method efficacy. The suggested method is based on fluorescent diagnostics of degree of accumulation of photosensibilizator in timorous tissue and the rate of its expenditure in process of performing of photodynamic therapy. There was made a comparison of parameters of methods and results of photodynamic therapy in 2 randomized groups. Each group consisted of 45 patients. The research method was applied in the main group and the standard method was used in the comparison group. It was found that the research method allowed significant reduction of duration of irradiation compared with conventional method (at the average from 690±65sec to 470±45sec, p=0,02), though the treatment results were the same. The suggested method allowed separation of group of patients with absence of fluorescence of timorous tissue. Performance of photodynamic therapy is unreasonable for these patients.
PurposeClinical outcome in patients with ischemic heart disease can be significantly improved with the implementation of targeted drug delivery into the ischemic myocardium. The purpose of this paper is to review the data of recent literature and present original findings relevant to the problem of therapeutic heart targeting with use of nanoparticles.Design/methodology/approachFor literature review, a public‐domain database (Medline) was searched using a web‐based search engine (PubMed) and the following key words: “nanoparticles”, “nanocarriers”, and “targeted drug delivery”. Experimental approaches included fabrication of carbon and silica nanoparticles, their characterization and surface modification. The acute hemodynamic effects of nanoparticle formulation as well as nanoparticle biodistribution were studied on male Wistar rats.FindingsCarbon and silica nanoparticles are biocompatible materials that can be used as carriers for heart‐targeted drug delivery. Concepts of passive and active targeting can be applied to the development of targeted drug delivery to the ischemic myocardial cells.Originality/valueThe present paper is believed to be the first on ligand‐directed targeted drug delivery into the damaged myocardium.
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