Evaluation of Targeted Delivery to the Brain Using Magnetic Immunoliposomes and Magnetic Force.

Magnetic nanoparticles have great prospects for drug delivery purposes, as they can be designed with various surface coatings and conjugated with drugs and targeting moieties. They also have a unique potential for precise delivery when guided by magnetic force. The blood-brain barrier (BBB) denotes the interface between the blood and brain parenchyma and hinders the majority of drugs from entering the brain. Red fluorescent magnetic nanoparticles were encapsulated in liposomes and conjugated to antibodies targeting the rat transferrin receptor (OX26) to form magnetic immunoliposomes. These magnetic immunoliposomes enhanced the uptake by rat brain capillary endothelial cells (BCECs) in vitro. In situ brain perfusion in young rats high in the endogenous expression of transferrin receptors by BCECs, revealed enhanced uptake of magnetic immunoliposomes when compared to naked magnetic nanoparticles or non-targeted magnetic liposomes. When applying the external magnetic force, the magnetic nanoparticles were detected in the brain parenchyma, suggesting transport across the BBB. Ultrastructural examination of the immunoliposomes, unfortunately, was unable to confirm a complete encapsulation of all naked nanoparticles within the liposomes, suggesting that the data on the brain could derive from particles being released from the liposomes under influence of external magnetic force; hence hypothesizes on external magnetic force as a qualifier for dragging targeted magnetic immunoliposomes through the BBB. In conclusion, our results suggest that transport of magnetic nanoparticles present in BCECs by targeted delivery to the transferrin receptor may undergo further transport into the brain when applying magnetic force. While magnetic immunoliposomes are targetable to BCECs, their design to enable further transport across the BBB when applying external magnetic force needs further improvement.

Serum Tau Fragments Predict Return to Play in Concussed Professional Ice Hockey Players.

The diagnosis of sports-related concussion is mainly based on subjective clinical symptoms and neuropsychological tests. Therefore, reliable brain injury biomarkers to assess when it is safe to return to play are highly desirable. The overall objective of this study was to evaluate the utility of two newly described tau fragments for diagnosis and prognosis of sports-related concussions. This multi-center prospective cohort study involved all 12 teams of the top professional ice hockey league in Sweden. A total of 288 players consented to participate in the study. Thirty-five players sustained concussions, of whom 28 underwent repeated blood samplings at 1, 12, 36, and 144 h after the trauma, or when the player returned to play (7 to >90 days). There was no significant increase in the levels of Tau-A in post-concussion samples compared with preseason values. However, serum levels of Tau-C were significantly higher in post-concussion samples compared with preseason. Further, levels of Tau-A correlated with the duration of post-concussive symptoms. Tau-A in serum, which is newly discovered biomarker, could be used to predict when it is safe to return to play after a sports-related concussion.

Development of a novel lipophilic, magnetic nanoparticle for in vivo drug delivery.

The aim of the present study was to evaluate the transfection potential of chitosan-coated, green-fluorescent magnetic nanoparticles (MNPs) (chi-MNPs) after encapsulation inside polyethylglycol (PEG)ylated liposomes that produced lipid-encapsulated chitosan-coated MNPs (lip-MNPs), and also to evaluate how these particles would distribute in vivo after systemic injection. The transfection potential of both chi-MNPs and lip-MNPs was evaluated in vitro in rat brain endothelial 4 (RBE4) cells with and without applying a magnetic field. Subsequently, the MNPs were evaluated in vivo in young rats. The in vitro investigations revealed that the application of a magnetic field resulted in an increased cellular uptake of the particles. The lip-MNPs were able to transfect the RBE4 cells with an incidence of approximately 20% of a commercial transfection agent. The in vivo distribution studies revealed that lip-MNPs had superior pharmacokinetic properties due to evasion of the RES, including hepatic Kuppfer cells and macrophages in the spleen. In conclusion, we were able to design a novel lipid-encapsulated MNP with the ability to carry genetic material, with favorable pharmacokinetic properties, and under the influence of a magnetic field with the capability to mediate transfection in vitro.

Brain delivery systems via mechanism independent of receptor-mediated endocytosis and adsorptive-mediated endocytosis.

The endothelial cells of the brain form the blood-brain barrier (BBB) that denotes a major restraint for drug entry to the brain. Traditional attempts to bypass the BBB have been by formulation of drugs with lipophilicity or low molecular weight designed to enable transport via solute nutrient transporters. The identification of many new targets in the brain cells form new ways of thinking drug design as modern therapeutics could be proteins and molecules of genetic origins like siRNA and cDNA that are prevented from entry into the brain unless encapsulated in drug carriers. In many chronic disorders affecting the central nervous system, the BBB is physically intact which further limits the entry of large molecules. The desirable entry of such molecules will be made by formulation of particular drug carriers that will enable their transport into the brain endothelium, or even through the endothelium and into the brain. This review discusses the potential of different principles for drug therapy to the brain with these main emphases on drug transport through the BBB: i) the effects of molecular lipidization, ii) the involvement of solute nutrient carriers, iii) targeted delivery using small peptides with high membrane penetrating properties, iv) treatment with magnetic nanoparticles. These different principles for therapy are also discussed with focus on possibilities of their improvement for targeted delivery to the brain.