Synthesis, Self-Assembly and In Vitro Cellular Uptake Kinetics of Nanosized Drug Carriers Based on Aggregates of Amphiphilic Oligomers of N-Vinyl-2-pyrrolidone

Development of nanocarrier-based drug delivery systems is a major breakthrough in pharmacology, promising targeted delivery and reduction in drug toxicity. On the cellular level, encapsulation of a drug substantially affects the endocytic processes due to nanocarrier–membrane interaction. In this study we synthesized and characterized nanocarriers assembled from amphiphilic oligomers of N-vinyl-2-pyrrolidone with a terminal thiooctadecyl group (PVP-OD). It was found that the dissolution free energy of PVP-OD depends linearly on the molecular mass of its hydrophilic part up to [Formula: see text] = 2 × 10(4), leading to an exponential dependence of critical aggregation concentration (CAC) on the molar mass. A model hydrophobic compound (DiI dye) was loaded into the nanocarriers and exhibited slow release into the aqueous phase on a scale of 18 h. Cellular uptake of the loaded nanocarriers and that of free DiI were compared in vitro using glioblastoma (U87) and fibroblast (CRL2429) cells. While the uptake of both DiI/PVP-OD nanocarriers and free DiI was inhibited by dynasore, indicating a dynamin-dependent endocytic pathway as a major mechanism, a decrease in the uptake rate of free DiI was observed in the presence of wortmannin. This suggests that while macropinocytosis plays a role in the uptake of low-molecular components, this pathway might be circumvented by incorporation of DiI into nanocarriers

Biodegradation of Polymers

В статье рассмотрены различные аспекты, связанные с получением, свойствами и применением полимеров, на основе которых создаются изделия, подвергающиеся распаду под действием биологических сред. Эти полимеры находят применение в медицине в качестве имплантатов и компонентов лекарственных систем; в биотехнологии – в качестве носителей в клеточной,тканевой и генной инженерии; в качестве упаковочных материалов, отходы которых распадаются в окружающей среде. Рассмотрены механизмы биодеградации, особенности взаимодействия биодеградируемых изделий и полимеров, из которых они изготовлены, с различными биологическими средами. Определены наиболее перспективные полимерные материалы, пригодные для создания биодеградируемых полимеров, и приведены некоторые сведения об их производствеThe paper discusses different aspects concerning obtaining, properties and application of appropriate biopolymers for making goods which are degrading under influence of biological media and applicable for medicine as implants and drug components, for biotechnology as carriers for cell, tissue and genetic engineering, and also for packaging materials destroying in the environment. Mechanisms of biodegradation, peculiarities of interconnection of biodegradable goods and their polymeric components with different biological media are considered. Most perspective polymeric materials for making biodegradable polymers are defined, and the information on their production is give

Biodegradation of Polymers

В статье рассмотрены различные аспекты, связанные с получением, свойствами и применением полимеров, на основе которых создаются изделия, подвергающиеся распаду под действием биологических сред. Эти полимеры находят применение в медицине в качестве имплантатов и компонентов лекарственных систем; в биотехнологии – в качестве носителей в клеточной,тканевой и генной инженерии; в качестве упаковочных материалов, отходы которых распадаются в окружающей среде. Рассмотрены механизмы биодеградации, особенности взаимодействия биодеградируемых изделий и полимеров, из которых они изготовлены, с различными биологическими средами. Определены наиболее перспективные полимерные материалы, пригодные для создания биодеградируемых полимеров, и приведены некоторые сведения об их производствеThe paper discusses different aspects concerning obtaining, properties and application of appropriate biopolymers for making goods which are degrading under influence of biological media and applicable for medicine as implants and drug components, for biotechnology as carriers for cell, tissue and genetic engineering, and also for packaging materials destroying in the environment. Mechanisms of biodegradation, peculiarities of interconnection of biodegradable goods and their polymeric components with different biological media are considered. Most perspective polymeric materials for making biodegradable polymers are defined, and the information on their production is give

Kinetics and Mechanism of Synthesis of Carboxyl-Containing N-Vinyl-2-Pyrrolidone Telehelics for Pharmacological Use

It was found that sulfanylethanoic and 3-sulfanylpropanoic acids are effective regulators of molecular weight with chain transfer constants of 0.441 and 0.317, respectively, and show an unexpected acceleration effect on the radical polymerization of N-vinyl-2-pyrrolidone, initiated by 2,2’-azobisisobutyronitrile. It was determined for the first time that the thiolate anions of mercapto acids form a high-temperature redox initiating system with 2,2’-azobisisobutyronitrile during the radical polymerization of N-vinyl-2-pyrrolidone in 1,4-dioxane. Considering the peculiarities of initiation, a kinetic model of the polymerization of N-vinyl-2-pyrrolidone is proposed, and it is shown that the theoretical orders of the reaction rate, with respect to the monomer, initiator, and chain transfer agent, are 1, 0.75, 0.25, and are close to their experimentally determined values. Carboxyl-containing techelics of N-vinyl-2-pyrrolidone were synthesized so that it can slow down the release of the anticancer drug, doxorubicin, from aqueous solutions, which can find its application in the pharmacological field

Mechanistic understanding of nanoparticles’ interactions with extracellular matrix: the cell and immune system

Abstract Extracellular matrix (ECM) is an extraordinarily complex and unique meshwork composed of structural proteins and glycosaminoglycans. The ECM provides essential physical scaffolding for the cellular constituents, as well as contributes to crucial biochemical signaling. Importantly, ECM is an indispensable part of all biological barriers and substantially modulates the interchange of the nanotechnology products through these barriers. The interactions of the ECM with nanoparticles (NPs) depend on the morphological characteristics of intercellular matrix and on the physical characteristics of the NPs and may be either deleterious or beneficial. Importantly, an altered expression of ECM molecules ultimately affects all biological processes including inflammation. This review critically discusses the specific behavior of NPs that are within the ECM domain, and passing through the biological barriers. Furthermore, regenerative and toxicological aspects of nanomaterials are debated in terms of the immune cells-NPs interactions

In Vitro Assessment of Poly-N-Vinylpyrrolidone/Acrylic Acid Nanoparticles Biocompatibility in a Microvascular Endothelium Model

An amphiphilic copolymer of N-vinyl-2-pyrrolidone and acrylic acid—namely, p(VP-AA)-OD6000 (p(VP-AA))—was synthesized to prepare p(VP-AA) nanoparticles (NPs). Furthermore, the copolymer was linked with CFSE, and the so-prepared nanoparticles were loaded with the DiI dye to form D nanoparticles (DNPs). In this study, as demonstrated by immunofluorescence microscopy, immunofluorescence, and confocal microscopy, DNPs were readily taken up by human microvascular endothelial cells (HMEC-1) cells in a concentration-dependent manner. Upon uptake, both the CFSE dye (green stain) and the DiI dye (red stain) were localized to the cytoplasm of treated cells. Treatment with p(VP-AA) did not affect the viability of normal and challenged with LPS, HMEC-1 cells at 0.010 mg/mL and induced a dose-dependent decrease of these cells’ viability at the higher concentrations of 0.033 and 0.066 mg/mL (p ≤ 0.01; p ≤ 0.001, respectively). Furthermore, we focused on the potential immunological activation of HMEC-1 endothelial cells upon p(VP-AA) NPs treatment by assessing the expression of adhesion molecules (E-Selectin, ICAM-1, and V-CAM). NPs treatments at concentrations utilized (p = NS) did not affect individual adhesion molecules’ expression. p(VP-AA) NPs do not activate the endothelium and do not affect its viability at pharmacologically relevant concentrations