Репозиторий Университета

© 2020 Wiley Periodicals LLC. Presently, most of anticancer drugs are high toxic for normal cells and, and as a result, they have severe side effects. Moreover, most of the formulations are lipophilic and have poor selectivity. To overcome these limitations, various drug delivery systems could be proposed. The aim of the current study was to fabricate novel polysaccharide nanocontainers (NC) by one-step ultrasonication technique and to evaluate their accumulation efficacy and cytotoxicity in 2D (monolayer culture) and 3D (tumor spheroids) in vitro models. NC with mean sizes in a range of 340–420 nm with the core-shell structure are synthetized and characterized. The NC shell is composed from diethylaminoethyl dextran/xanthan gum polyelectrolyte complex, while the hydrophobic core was loaded with the lipophilic anticancer drug thymoquinone. To enhance NC accumulation in human breast adenocarcinoma MCF-7 cells, the NC surface was modified with poly-L-lysine (PLL) or polyethylene glycol. Cell uptake of the NC loaded with Nile Red into the tumor cells was investigated by laser scanning confocal microscopy, fluorescent flow cytometry and fluorimetry. Modification of the NC with PLL allowed to obtain the optimal drug delivery system with maximal cytotoxicity, which was tested by MTT-test. The developed NC are promising for lipophilic anticancer drug delivery.

© 2020 Wiley Periodicals LLC. Presently, most of anticancer drugs are high toxic for normal cells and, and as a result, they have severe side effects. Moreover, most of the formulations are lipophilic and have poor selectivity. To overcome these limitations, various drug delivery systems could be proposed. The aim of the current study was to fabricate novel polysaccharide nanocontainers (NC) by one-step ultrasonication technique and to evaluate their accumulation efficacy and cytotoxicity in 2D (monolayer culture) and 3D (tumor spheroids) in vitro models. NC with mean sizes in a range of 340–420 nm with the core-shell structure are synthetized and characterized. The NC shell is composed from diethylaminoethyl dextran/xanthan gum polyelectrolyte complex, while the hydrophobic core was loaded with the lipophilic anticancer drug thymoquinone. To enhance NC accumulation in human breast adenocarcinoma MCF-7 cells, the NC surface was modified with poly-L-lysine (PLL) or polyethylene glycol. Cell uptake of the NC loaded with Nile Red into the tumor cells was investigated by laser scanning confocal microscopy, fluorescent flow cytometry and fluorimetry. Modification of the NC with PLL allowed to obtain the optimal drug delivery system with maximal cytotoxicity, which was tested by MTT-test. The developed NC are promising for lipophilic anticancer drug delivery.

© 2020 Biosensors based on nanotechnology are developing rapidly and are widely applied in many fields including biomedicine, environmental monitoring, national defense and analytical chemistry, and have achieved vital positions in these fields. Novel nano-materials are intensively developed and manufactured for potential biosensing and theranostic applications while lacking comprehensive assessment of their potential health risks. The integration of diagnostic in vivo biosensors and the DDSs for delivery of therapeutic drugs holds an enormous potential in next-generation theranostic platforms. Controllable, precise, and safe delivery of diagnostic biosensing devices and therapeutic agents to the target tissues, organs, or cells is an important determinant in developing advanced nanobiosensor-based theranostic platforms. Particularly, inspired by the comprehensive biological investigations on the red blood cells (RBCs), advanced strategies of RBC-mediated in vivo delivery have been developed rapidly and are currently in different stages of transforming from research and design to pre-clinical and clinical investigations. In this review, the RBC-mediated delivery of in vivo nanobiosensors for applications of bio-imaging at the single-cell level, advanced medical diagnostics, and analytical detection of biomolecules and cellular activities are presented. A comprehensive perspective of the technical framework of the state-of-the-art RBC-mediated delivery systems is explained in detail to inspire the design and implementation of advanced nanobiosensor-based theranostic platforms taking advantage of RBC-delivery modalities.

© 2020 Elsevier Ltd COVID-19, coronavirus disease 2019, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a pandemic. At the time of writing this (October 14, 2020), more than 38.4 million people have become affected, and 1.0 million people have died across the world. The death rate is undoubtedly correlated with the cytokine storm and other pathological pulmonary characteristics, as a result of which the lungs cannot provide sufficient oxygen to the body's vital organs. While diversified drugs have been tested as a first line therapy, the complexity of fatal cases has not been reduced so far, and the world is looking for a treatment to combat the virus. However, to date, and despite such promise, we have received very limited information about the potential of nanomedicine to fight against COVID-19 or as an adjunct therapy in the treatment regimen. Over the past two decades, various therapeutic strategies, including direct-acting antiviral drugs, immunomodulators, a few non-specific drugs (simple to complex), have been explored to treat Acute Respiratory Distress Syndrome (ARDS), Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS), influenza, and sometimes the common flu, thus, correlating and developing specific drugs centric to COVID-19 is possible. This review article focuses on the pulmonary pathology caused by SARS-CoV-2 and other viral pathogens, highlighting possible nanomedicine therapeutic strategies that should be further tested immediately.

© 2020 Elsevier Ltd COVID-19, coronavirus disease 2019, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a pandemic. At the time of writing this (October 14, 2020), more than 38.4 million people have become affected, and 1.0 million people have died across the world. The death rate is undoubtedly correlated with the cytokine storm and other pathological pulmonary characteristics, as a result of which the lungs cannot provide sufficient oxygen to the body's vital organs. While diversified drugs have been tested as a first line therapy, the complexity of fatal cases has not been reduced so far, and the world is looking for a treatment to combat the virus. However, to date, and despite such promise, we have received very limited information about the potential of nanomedicine to fight against COVID-19 or as an adjunct therapy in the treatment regimen. Over the past two decades, various therapeutic strategies, including direct-acting antiviral drugs, immunomodulators, a few non-specific drugs (simple to complex), have been explored to treat Acute Respiratory Distress Syndrome (ARDS), Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS), influenza, and sometimes the common flu, thus, correlating and developing specific drugs centric to COVID-19 is possible. This review article focuses on the pulmonary pathology caused by SARS-CoV-2 and other viral pathogens, highlighting possible nanomedicine therapeutic strategies that should be further tested immediately.

© 2020 Elsevier B.V. Photosensitive polymeric three-dimensional microstructured film (PTMF) is a new type of patterned polymeric films functionalized with an array of sealed hollow 3D containers. The microstructured system with enclosed chemicals provides a tool for the even distribution of biologically active substances on a given surface that can be deposited on medical implants or used as a cells substrate. In this work, we proposed a way for photothermally activating and releasing encapsulated substances at picogram amounts from the PTMF surface in different environments using laser radiation delivered with a multimode optical fiber. The photosensitive PTMFs were prepared by the layer-by-layer (LbL) assembly from alternatively charged polyelectrolytes followed by covering with a layer of hydrophobic polylactic acid (PLA) and a layer of gold nanoparticles (AuNPs). Moreover, the typical photothermal cargo release amounts were determined on the surface of the PTMF for a range of laser powers delivered to films placed in the air, deionized (DI) water, and 1% agarose gel. The agarose gel was used as a soft tissue model for developing a technique for the laser activation of PTMFs deep in tissues using optical waveguides. The number of PTMF chambers activated by a near-infrared (NIR) laser beam was evaluated as the function of optical parameters.

© 2020 Elsevier B.V. Photosensitive polymeric three-dimensional microstructured film (PTMF) is a new type of patterned polymeric films functionalized with an array of sealed hollow 3D containers. The microstructured system with enclosed chemicals provides a tool for the even distribution of biologically active substances on a given surface that can be deposited on medical implants or used as a cells substrate. In this work, we proposed a way for photothermally activating and releasing encapsulated substances at picogram amounts from the PTMF surface in different environments using laser radiation delivered with a multimode optical fiber. The photosensitive PTMFs were prepared by the layer-by-layer (LbL) assembly from alternatively charged polyelectrolytes followed by covering with a layer of hydrophobic polylactic acid (PLA) and a layer of gold nanoparticles (AuNPs). Moreover, the typical photothermal cargo release amounts were determined on the surface of the PTMF for a range of laser powers delivered to films placed in the air, deionized (DI) water, and 1% agarose gel. The agarose gel was used as a soft tissue model for developing a technique for the laser activation of PTMFs deep in tissues using optical waveguides. The number of PTMF chambers activated by a near-infrared (NIR) laser beam was evaluated as the function of optical parameters.

© 2020 Elsevier B.V. Photosensitive polymeric three-dimensional microstructured film (PTMF) is a new type of patterned polymeric films functionalized with an array of sealed hollow 3D containers. The microstructured system with enclosed chemicals provides a tool for the even distribution of biologically active substances on a given surface that can be deposited on medical implants or used as a cells substrate. In this work, we proposed a way for photothermally activating and releasing encapsulated substances at picogram amounts from the PTMF surface in different environments using laser radiation delivered with a multimode optical fiber. The photosensitive PTMFs were prepared by the layer-by-layer (LbL) assembly from alternatively charged polyelectrolytes followed by covering with a layer of hydrophobic polylactic acid (PLA) and a layer of gold nanoparticles (AuNPs). Moreover, the typical photothermal cargo release amounts were determined on the surface of the PTMF for a range of laser powers delivered to films placed in the air, deionized (DI) water, and 1% agarose gel. The agarose gel was used as a soft tissue model for developing a technique for the laser activation of PTMFs deep in tissues using optical waveguides. The number of PTMF chambers activated by a near-infrared (NIR) laser beam was evaluated as the function of optical parameters.

© 2019 by the authors. Licensee MDPI, Basel, Switzerland. There is a pressing clinical need for advanced colon-specific local drug delivery systems that can provide major advantages in treating diseases associated with the colon, such as inflammatory bowel disease (IBD) and colon cancer. A precise colon targeted drug delivery platform is expected to reduce drug side effects and increase the therapeutic response at the intended disease site locally. In this study, we report the fabrication of hyaluronan (HA) functionalized polymeric hybrid nanoparticulate system (Cur-HA NPs) by using curcumin as a model fluorescent drug. The Cur-HA NPs were about 200–300 nm in size, −51.3 mV overall surface charge after HA functionalization, with 56.0% drug released after 72 h in simulated gastrointestinal fluids. The Cur-HA NPs did not exhibit any cytotoxicity by AlamarBlue, PicoGreen and Live/Dead assays. Following the Cur-HA NPs use on HT-29 monolayer cell cultures demonstrating, the efficacy of HA functionalization increases cellular interaction, uptake when compared to uncoated nanoparticulate system. These findings indicate that HA functionalized nano-hybrid particles are effective in delivering drugs orally to the lower gastrointestinal tract (GIT) in order to treat local colonic diseases.

© 2019 American Pharmacists Association® Various drug delivery systems (DDSs) are often used in modern medicine to achieve controlled and targeted drug release. Diffusional release of drugs from DDSs is often the main mechanism, especially at early times. Generally, average dimensions of DDS are used to model the drug release, but our recent work on drug release from fibers demonstrated that taking into account diameter distribution is essential. This work systematically investigated the effect of size distribution on diffusional drug release from DDSs of various geometric forms such as membranes, fibers, and spherical particles. The investigation clearly demonstrated that the size distribution has the largest effect on the drug release profiles from spherical particles compared to other geometric forms. Published experimental data for drug release from polymer microparticles and nanoparticles were fitted, and the diffusion coefficients were determined assuming reported radius distributions. Assuming the average radius when fitting the data leads to up to 5 times underestimation of the diffusion coefficient of drug in the polymer.

©2018 by the authors. Licensee MDPI, Basel, Switzerland. Engineering of a “smart” drug delivery system to specifically target tumour cells has been at the forefront of cancer research, having been engineered for safer, more efficient and effective use of chemotherapy for the treatment of cancer. However, selective targeting and choosing the right cancer surface biomarker are critical for a targeted treatment to work. Currently, the available delivery systems use a two-dimensional monolayer of cancer cells to test the efficacy of the drug delivery system, but designing a “smart” drug delivery system to be specific for a tumour in vivo and to penetrate the inner core remains a major design challenge. These challenges can be overcome by using a study model that integrates the three-dimensional aspect of a tumour in a culture system. Here, we tested the efficacy of a functionalized folic acid-conjugated amphiphilic alternating copolymer poly(styrene-alt-maleic anhydride) (FA-DABA-SMA) via a biodegradable linker 2,4-diaminobutyric acid (DABA) to specifically target and penetrate the inner core of three-dimensional avascular human pancreatic and breast tumour spheroids in culture. The copolymer was quantitatively analyzed for its hydrophobic drug encapsulation efficiency using three different chemical drug structures with different molecular weights. Their release profiles and tumour targeting properties at various concentrations and pH environments were also characterized. Using the anticancer drug curcumin and two standard clinical chemotherapeutic hydrophobic drugs, paclitaxel and 5-fluorouracil, we tested the ability of FA-DABA-SMA nanoparticles to encapsulate the differently sized drugs and deliver them to kill monolayer pancreatic cancer cells using the WST-1 cell proliferation assay. The findings of this study revealed that the functionalized folic acid-conjugated amphiphilic alternating copolymer shows unique properties as an active “smart” tumor-targeting drug delivery system with the ability to internalize hydrophobic drugs and release the chemotherapeutics for effective killing of cancer cells. The novelty of the study is the first to demonstrate a functionalized “smart” drug delivery system encapsulated with a hydrophobic drug effectively targeting and penetrating the inner core of pancreatic and breast cancer spheroids and reducing their volumes in a dose-and time-dependent manner.

© 2018, Springer Science+Business Media, LLC, part of Springer Nature. The liposomal form of silibinin was obtained, and its antihepatotoxic activity in mice was studied using a model of acute toxic hepatitis caused by injection of carbon tetrachloride or paracetamol. It was shown that the use of the drug in therapy or prevention regimens leads to normalization of levels of transaminases and total protein in the blood of experimental animals. The results of the study showed that liposomal silibinin when administered intravenously shows a more pronounced hepatoprotective effect compared to intragastric administration of free silibinin. Thus, the effectiveness of the therapeutic action of silibinin can be significantly increased by using its liposomal form. Liposomal drug, in contrast to native silibinin, can be injected directly into the blood that significantly increases its bioavailability.

© 2018 Elsevier B.V. The mathematical model describing drug flux through microporated skin was previously developed. Based on this model, two mathematical equations can be used to predict the microporatio-enhanced transdermal drug flux: the complex primal equation containing a variety of experimentally-determined variables, and the simplified straightforward equation. In this study, experimental transdermal fluxes of three corticosteroids through split-thickness human skin treated with a microneedle roller were measured, and the values of fluxes compared with those predicted using both the more complex and simplified equations. According to the results of the study, both equations demonstrated high accuracy in the prediction of the fluxes of corticosteroids. The simplified equation was validated and confirmed as robust using regression analysis of literature data. Further, its capability and ease of use was exemplified by predicting the flux of methotrexate through the skin microporated with laser and comparing with published experimental data.

© 2017 Elsevier B.V. Microneedles is the technique of drug delivery enhancement, which was primarily designed for facilitating percutaneous drug delivery. Started from the development of simple solid microneedles, providing microporation of stratum corneum and therefore enhancement of topical drug delivery, for two decades the technique has progressed in various modifications such as hollow, coated, dissolving and hydrogel forming microneedles. In their turn, the modifications have resulted in new mechanisms of drug delivery enhancement and followed by the expansion of applicability range in terms of targeted tissues and organs. Thus, in addition to percutaneous drug delivery, microneedles have been considered as an efficient technique facilitating ocular, oral mucosal, gastrointestinal, ungual and vaginal drug administration. It is anticipated that the technique of microneedle-assisted drug delivery will soon become relevant for majority of organs and tissues.