Kohdennetut nanolääkkeet voivat muokata tulevaisuuden terveydenhoitoa

Kohdennettu nanolääke on nanokokoisen kantajahiukkasen ja lääkeainemolekyylin yhdistelmä. Tällaisten lääkkeiden etu tavanomaisiin lääkkeisiin nähden on se, että ne voivat kuljettaa lääkkeet oikeaan kudokseen tai soluun ja vapauttaa ne vasta siellä. Ideaaliset nanolääkkeet ovat yhteensopivia kudosten kanssa (bioyhteensopivia) ja biohajoavia. Ne voivat tunkeutua syvälle syöpäkudokseen ja niitä voidaan muokata siten, että ne kiinnittyvät vain tiettyihin kohdesoluihin. Ensimmäinen nanolääkesukupolvi on jo markkinoilla, ja seuraavia tutkitaan kliinisissä kokeissa.Kohdennettu nanolääke on nanokokoisen kantajahiukkasen ja lääkeainemolekyylin yhdistelmä. Tällaisten lääkkeiden etu tavanomaisiin lääkkeisiin nähden on se, että ne voivat kuljettaa lääkkeet oikeaan kudokseen tai soluun ja vapauttaa ne vasta siellä. Ideaaliset nanolääkkeet ovat yhteensopivia kudosten kanssa (bioyhteensopivia) ja biohajoavia. Ne voivat tunkeutua syvälle syöpäkudokseen ja niitä voidaan muokata siten, että ne kiinnittyvät vain tiettyihin kohdesoluihin. Ensimmäinen nanolääkesukupolvi on jo markkinoilla, ja seuraavia tutkitaan kliinisissä kokeissa.Peer reviewe

One-step microfluidics production of enzyme-loaded liposomes for the treatment of inflammatory diseases

The biopharmaceuticals market is constantly growing. Despite their advantages over the conventional drugs, biopharmaceuticals have short biological half-lifes, which can be increased using liposomes. However, the common bulk methods to produce biopharmaceuticals-loaded liposomes result in lost of encapsulation efficiency (E.E.), resulting in an expensive process. Herein, the encapsulation of a therapeutic enzyme in liposomes is proposed, using a glass-capillary microfluidic technique. Cu,Zn- Superoxide dismutase (SOD) is successfully encapsulated into liposomes (SOD@Liposomes). SOD@Liposomes with a mean size of 135 ± 41 nm, a polydispersity index of 0.13 ± 0.01, an E.E. of 59 ± 6 % and an enzyme activity of 82 ± 3 % are obtained. In vivo experiments show, through an ear edema model, that SOD@Liposomes administered by the intravenous route enable an edema inhibition of 65 % ± 8 %, over the 20 % ± 13 % of SOD in its free form. The histopathological analyses show a higher inflammatory cell accumulation on the ear treated with SOD in its free form, than treated with SOD@Liposomes. Overall, this work highlights the potential of microfluidics for the production of enzyme-loaded liposomes with high encapsulation efficiency, with the intrinsic advantages of the low time-consuming and easily upscaling microfluidic assembly method.Peer reviewe

pH and Reactive Oxygen Species-Sequential Responsive Nano-in-Micro Composite For Targeted Therapy of Inflammatory Bowel Disease

Oxidative stress and abnormally high levels of reactive oxygen species (ROS) play an essential role in the pathogenesis and progression of inflammatory bowel disease (IBD). Oxidation‐responsive nanoparticles (NPs) are formulated from a phenylboronic esters‐modified dextran (OxiDEX) that degrades selectively in response to hydrogen peroxide (H2O2). OxiDEX NPs are coated with chitosan and encapsulated in a pH‐sensitive polymer to produce nano‐in‐micro composites. The microparticles are spherical with homogeneous particle size (53 ± 3 µm) and maintain integrity at acidic pH, preventing the premature release of the NPs in gastric conditions. The degradation of NPs is highly responsive to the level of H2O2, and the release of the drug is sustained in the presence of physiologically relevant H2O2 concentrations. The presence of chitosan on the particles surface significantly enhances NPs stability in intestinal pH and their adhesion on the intestinal mucosa. Compared to a traditional enteric formulation, this formulation shows tenfold decreased drug permeability across C2BBe1/HT29‐MTX cell monolayer, implying that lower amount of drug would be absorbed to the blood stream and, therefore, limiting the undesired systemic side effects. Based on these results, a successful nano‐in‐micro composite for targeted therapy of IBD is obtained by combination of the responsiveness to pH and ROS.Peer reviewe

Preparation and In vivo Evaluation of Red Blood Cell Membrane Coated Porous Silicon Nanoparticles Implanted with 155Tb

Introduction Porous silicon (PSi) nanoparticles are capable of delivering therapeutic payloads providing targeted delivery and sustained release of the payloads. In this work we describe the development and proof-of-concept in vivo evaluation of thermally hydrocarbonized porous silicon (PSi) nanoparticles that are implanted with radioactive 155Tb atoms and coated with red blood cell (RBC) membrane (155Tb-THCPSi). The developed nanocomposites can be utilized as an intravenous delivery platform for theranostic radionuclides. Methods THCPSi thin films were implanted with 155Dy ions that decay to 155Tb at the ISOLDE radioactive ion-beam (RIB) facility at CERN. The films were processed to nanoparticles by ball-milling and sonication, and subsequently coated with either a solid lipid and RBC membrane or solely with RBC membrane. The nanocomposites were evaluated in vitro for stability and in vivo for circulation half-life and ex vivo for biodistribution in Balb/c mice. Results Nanoporous THCPSi films were successfully implanted with 155Tb and processed to coated nanoparticles. The in vitro stability of the particles in plasma and buffer solutions was not significantly different between the particle types, and therefore the RBC membrane coated particles with less laborious processing method were chosen for the biological evaluation. The RBC membrane coating enhanced significantly the blood half-life compared to bare THCPSi particles. In the ex vivo biodistribution study a pronounced accumulation to the spleen was found, with lower uptake in the liver and a minor uptake in the lung, gall bladder and bone marrow. Conclusions We have demonstrated, using 155Tb RIB-implanted PSi nanoparticles coated with mouse RBC membranes, the feasibility of using such a theranostic nanosystem for the delivery of RIB based radionuclides with prolonged circulation time. Advances in Knowledge and Implications for Patient Care: For the first time, the RIB implantation technique has been utilized to produce PSi nanoparticle with a surface modified for better persistence in circulation. When optimized, these particles could be used in targeted radionuclide therapy with a combination of chemotherapeutic payload within the PSi structure.Peer reviewe

Manipulating Superparamagnetic Microparticles with an Electromagnetic Needle

Selective, precise, and high-throughput manipulation of individual superparamagnetic microparticles has profound applications in performing location-tailored in vitro biomedical studies. The current techniques for manipulation of microparticles allow only a single particle in the manipulation workspace, or simultaneous transportation of multiple microparticles in batches. In this work, a method based on a robotized electromagnetic needle for manipulation of individual superparamagnetic microparticles within a microparticle population is introduced. By automatically controlling the highly localized magnetic field of the needle, a single microparticle is selectively picked when its neighboring particle is few micrometers away. Supported by the nanometer resolution of the robotic positioner, particles are placed at sub-micrometer precision. This manipulation technique allows the creating of arbitrary patterns, sorting of microparticles based on size and morphology, and transporting of individual microparticles in 3D space. Therefore, this approach has the potential to enable more deterministic and quantitative microanalysis and microsynthesis using superparamagnetic microparticles.Peer reviewe