Nanoparticle-Mediated Drug Delivery: Blood-Brain Barrier as the Main Obstacle to Treating Infectious Diseases in CNS

Abstract

Background: Parasitic infections affecting the central nervous system (CNS) present high morbidity and mortality rates and affect millions of people worldwide. The most important parasites affecting the CNS are protozoans (Plasmodium sp., Toxoplasma gondii, Trypanosoma brucei), cestodes (Taenia solium) and free-living amoebae (Acantamoeba spp., Balamuthia mandrillaris and Naegleria fowleri). Current therapeutic regimens include the use of traditional chemicals or natural compounds that have very limited access to the CNS, despite their elevated toxicity to the host. Improvements are needed in drug administration and formulations to treat these infections and to allow the drug to cross the blood-brain barrier (BBB). Methods: This work aims to elucidate the recent advancements in the use of nanoparticles as nanoscaled drug delivery systems (NDDS) for treating and controlling the parasitic infections that affect the CNS, addressing not only the nature and composition of the polymer chosen, but also the mechanisms by which these nanoparticles may cross the BBB and reach the infected tissue. Results: There is a strong evidence in the literature demonstrating the potential usefulness of polymeric nanoparticles as functional carriers of drugs to the CNS. Some of them demonstrated the mechanisms by which drugloaded nanoparticles access the CNS and control the infection by using in vivo models, while others only describe the pharmacological ability of these particles to be utilized in in vitro environments. Conclusion: The scarcity of the studies trying to elucidate the compatibility as well as the exact mechanisms by which NDDS might be entering the CNS infected by parasites reveals new possibilities for further exploratory projects. There is an urgent need for new investments and motivations for applying nanotechnology to control parasitic infectious diseases worldwide.

Ultrasound-responsive polymer-based drug delivery systems

“…Other kinds of infectious diseases that are hard to treat are parasitic infections in the central nervous system. Polymeric nanoparticles have shown to be effective for the treatment of such diseases [153,154]. As discussed in "Disruption of blood-brain barrier" section, ultrasound-responsive polymeric carriers are able to deliver drugs across the BBB [30].…”

Deciphering the role of nanoparticles for management of bacterial meningitis: an update on recent studies

“…BBB is a network that consists of a complicated system of endothelial cells, astroglia, pericytes, and perivascular mast cells that block most circulating cells and molecules from moving through (Gondim et al 2019 ). The BBB is extremely selective and has unique transport mechanisms that permit molecules or cells to access the parenchyma of the brain to be closely regulated (Ebrahimi et al 2020 ).…”

“…Tight junctions (TJs) have two functions: (i) they block small molecules and ions from moving via the space among cells, causing them to reach the cells (by diffusion or active transport). This pathway regulates the types and quantities of substances that can move through it; (ii) they stop vital membrane proteins from moving between the cells of apical and basolateral membranes, allowing each of the cells of membrane surfaces to maintain their distinct functions, such as receptor-mediated endocytosis at the apical surface and exocytosis at the basolateral surface (Gondim et al 2019 ). Tight junctions that have become loose allow nanoparticles to pass across the BBB; either due to the existence of a surfactant in the NPs that can interrupt the TJs.…”

Fluorescent Markers: Proteins and Nanocrystals

“…[39,[50][51][52] The bioconjugation allows the study and tracking of biomolecules in biological systems such as cell cultures and laboratory animals. [53,54] The versatility of QDs associated with maltosebinding protein for intracellular delivery of the drug beta-cyclodextrin. [55] Other studies have used the quantum dots for in vivo multiphoton biologic imaging.…”