Studies on Aggregated Nanoparticles Steering during Deep Brain Membrane Crossing

Many central nervous system (CNS) diseases, such as Alzheimer’s disease (AD), affect the deep brain region, which hinders their effective treatment. The hippocampus, a deep brain area critical for learning and memory, is especially vulnerable to damage during early stages of AD. Magnetic drug targeting has shown high potential in delivering drugs to a targeted disease site effectively by applying a strong electromagnetic force. This study illustrates a nanotechnology-based scheme for delivering magnetic nanoparticles (MNP) to the deep brain region. First, we developed a mathematical model and a molecular dynamic simulation to analyze membrane crossing, and to study the effects of particle size, aggregation, and crossing velocities. Then, using in vitro experiments, we studied effective parameters in aggregation. We have also studied the process and environmental parameters. We have demonstrated that aggregation size can be controlled when particles are subjected to external electromagnetic fields. Our simulations and experimental studies can be used for capturing MNPs in brain, the transport of particles across the intact BBB and deep region targeting. These results are in line with previous in vivo studies and establish an effective strategy for deep brain region targeting with drug loaded MNPs through the application of an external electromagnetic field.

Magnetically Assisted Drug Delivery of Topical Eye Drops Maintains Retinal Function In Vivo in Mice

Barded-Biedl syndrome (BBS) is a rare genetic disorder with an unmet medical need for retinal degeneration. Small-molecule drugs were previously identified to slow down the apoptosis of photoreceptors in BBS mouse models. Clinical translation was not practical due to the necessity of repetitive invasive intravitreal injections for pediatric populations. Non-invasive methods of retinal drug targeting are a prerequisite for acceptable adaptation to the targeted pediatric patient population. Here, we present the development and functional testing of a non-invasive, topical, magnetically assisted delivery system, harnessing the ability of magnetic nanoparticles (MNPs) to cargo two drugs (guanabenz and valproic acid) with anti-unfolded protein response (UPR) properties towards the retina. Using magnetic resonance imaging (MRI), we showed the MNPs’ presence in the retina of Bbs wild-type mice, and their photoreceptor localization was validated using transmission electron microscopy (TEM). Subsequent electroretinogram recordings (ERGs) demonstrated that we achieved beneficial biological effects with the magnetically assisted treatment translating the maintained light detection in Bbs−/− mice (KO). To our knowledge, this is the first demonstration of efficient magnetic drug targeting in the photoreceptors in vivo after topical administration. This non-invasive, needle-free technology expands the application of SMDs for the treatment of a vast spectrum of retinal degenerations and other ocular diseases.

SPIONs and magnetic hybrid materials: Synthesis, toxicology and biomedical applications

In the past decades, a wide variety of different superparamagnetic iron oxide nanoparticles (SPIONs) have been synthesized. Due to their unique properties, such as big surface-to-volume ratio, superparamagnetism and comparatively low toxicity, they are principally well suited for many different technical and biomedical applications. Meanwhile, there are a numerous synthesis methods for SPIONs, but high requirements for biocompatibility have so far delayed a successful translation into the clinic. Moreover, depending on the planned application, such as for imaging, magnetic drug targeting, hyperthermia or for hybrid materials intended for regenerative medicine, specific physicochemical and biological properties are inevitable. Since a summary of all existing SPION systems, their properties and application is far too extensive, this review reports on selected methods for SPION synthesis, their biocompatibility and biomedical applications.

Recent Advances in the Development of Magnetic Nanoparticles for Biomedical Applications

The unique properties of magnetic nanoparticles have led them to be considered materials with significant potential in the biomedical field. Nanometric size, high surface-area ratio, ability to function at molecular level, exceptional magnetic and physicochemical properties, and more importantly, the relatively easy tailoring of all these properties to the specific requirements of the different biomedical applications, are some of the key factors of their success. In this paper, we will provide an overview of the state of the art of different aspects of magnetic nanoparticles, specially focusing on their use in biomedicine. We will explore their magnetic properties, synthetic methods and surface modifications, as well as their most significative physicochemical properties and their impact on the in vivo behaviour of these particles. Furthermore, we will provide a background on different applications of magnetic nanoparticles in biomedicine, such as magnetic drug targeting, magnetic hyperthermia, imaging contrast agents or theranostics. Besides, current limitations and challenges of these materials, as well as their future prospects in the biomedical field will be discussed.

Nonviral Locally Injected Magnetic Vectors for In Vivo Gene Delivery: A Review of Studies on Magnetofection

Magnetic nanoparticles have been widely used in nanobiomedicine for diagnostics and the treatment of diseases, and as carriers for various drugs. The unique magnetic properties of “magnetic” drugs allow their delivery in a targeted tumor or tissue upon application of a magnetic field. The approach of combining magnetic drug targeting and gene delivery is called magnetofection, and it is very promising. This method is simple and efficient for the delivery of genetic material to cells using magnetic nanoparticles controlled by an external magnetic field. However, magnetofection in vivo has been studied insufficiently both for local and systemic routes of magnetic vector injection, and the relevant data available in the literature are often merely descriptive and contradictory. In this review, we collected and systematized the data on the efficiency of the local injections of magnetic nanoparticles that carry genetic information upon application of external magnetic fields. We also investigated the efficiency of magnetofection in vivo, depending on the structure and coverage of magnetic vectors. The perspectives of the development of the method were also considered.