Remote navigation and targeted delivery of biologically active compounds is one of the current challenges in the development of drug delivery systems. Modern methods of micro- and nanofabrication give us new opportunities to produce particles and capsules bearing cargo to deploy and possess magnetic properties to be externally navigated. In this work we explore multilayer composite magnetic microcapsules as targeted delivery systems in vitro and in vivo studies under natural conditions of living organism. Herein, we demonstrate magnetic addressing of fluorescent composite microcapsules with embedded magnetite nanoparticles in blood flow environment. First, the visualization and capture of the capsules at the defined blood flow by the magnetic field are shown in vitro in an artificial glass capillary employing a wide-field fluorescence microscope. Afterward, the capsules are visualized and successfully trapped in vivo into externally exposed rat mesentery microvessels. Histological analysis shows that capsules infiltrate small mesenteric vessels whereas large vessels preserve the blood microcirculation. The effect of the magnetic field on capsule preferential localization in bifurcation areas of vasculature, including capsule retention at the site once external magnet is switched off is discussed. The research outcome demonstrates that microcapsules can be effectively addressed in a blood flow, which makes them a promising delivery system with remote navigation by the magnetic field.
We demonstrate a novel approach to the controlled loading of inorganic nanoparticles and proteins into submicron- and micron-sized porous particles. The approach is based on freezing/thawing cycles, which lead to high loading densities. The process was tested for the inclusion of Au, magnetite nanoparticles, and bovine serum albumin in biocompatible vaterite carriers of micron and submicron sizes. The amounts of loaded nanoparticles or substances were adjusted by the number of freezing/thawing cycles. Our method afforded at least a three times higher loading of magnetite nanoparticles and a four times higher loading of protein for micron vaterite particles, in comparison with conventional methods such as adsorption and coprecipitation. The capsules loaded with magnetite nanoparticles by the freezing-induced loading method moved faster in a magnetic field gradient than did the capsules loaded by adsorption or coprecipitation. Our approach allows the preparation of multicomponent nanocomposite materials with designed properties such as remote control (e.g. via the application of an electromagnetic or acoustic field) and cargo unloading. Such materials could be used as multimodal contrast agents, drug delivery systems, and sensors.
Polyelectrolyte (PE) and nanocomposite (NC) microcapsules fabricated by layer‐by‐layer technique have been of great interest in the past decade as novel entities for cargo encapsulation and delivery as well as for diagnostic purposes. The unique physicochemical properties of polymers and inorganic nanoparticles used in layer‐by‐layer synthesis of PE and NC microcapsules make them promising in various fields, such as storage, catalysis, cells imaging, controlled drug release, and targeted drug delivery. However, the requirement of the cargo encapsulation is that the cargo should have a relatively large molecular weight in order to avoid the leakage from the capsules. In this review, recent progress in the design and functionalization of PE and NC microcapsules using sol–gel method for storage of small cargos have been presented. Moreover, various remote exposures on the permeability of organic/inorganic composite microcapsule shells such as ultrasound, magnetic field gradient, laser, and microwave radiation have been observed. Finally, the description and discussion of the new trends and perspectives for improved functionality of PE microcapsules are the major topic of this progress report.
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