An Insight to Brain Targeting Utilizing Polymeric Nanoparticles: Effective Treatment Modalities for Neurological Disorders and Brain Tumor

Abstract

The delivery of therapeutic molecules to the brain remains an unsolved problem to the researchers due to the existence of the blood–brain barrier (BBB), which halts the entry of unwanted substances to the brain. Central nervous system (CNS) disorders, mainly Parkinson’s disease, Alzheimer’s disease, schizophrenia, brain tumors, and stroke, are highly prevalent globally and are a growing concern for researchers due to restricting the delivery of pharmaceutical drugs to the brain. So effective treatment modalities are essential to combat the growing epidemic of CNS diseases. Recently, the growing attention in the field of nanotechnology has gained the faith of researchers for the delivery of therapeutics to the brain by targeting them to the specific target site. Polymeric nanoparticles (PNPs) emerge out to be an instrumental approach in drug targeting to the brain by overcoming the physiological barrier, biomedical barrier, and BBB. Preclinical discovery has shown the tremendous potential and versatility of PNPs in encapsulating several drugs and their targeting to the deepest regions of the brain, thus improving therapeutic intervention of CNS disorders. The current review will summarize advances in the development of PNPs for targeting therapeutics to the brain and the functional and molecular effects obtained in the preclinical model of most common CNS diseases. The advancement of PNPs in clinical practice and their prospect in brain targeting will also be discussed briefly.

Intranasal Polymeric and Lipid-Based Nanocarriers for CNS Drug Delivery

“…These ligands include transferrin, lactoferrin, apolipoprotein E, glucose derivatives, and glutathione, which facilitate the brain uptake of NPs through receptor-mediated transcytosis and carrier-mediated transport mechanisms [ 36 ]. Cell-penetrating peptides (CPPs) like the transactivator of transcription can also be bound to the surface of NPs through covalent or non-covalent interactions [ 8 ]. Conjugation with CPPs can enhance transport through cell membranes, increasing BBB crossing and cellular uptake of drug-loaded NPs [ 40 ].…”

“…The materials used and the physicochemical properties of nano formulations, such as their shape, size, and surface charge can be tailored according to their purpose [ 6 ]. Polymeric and lipid-based nanoparticles (NPs) are emerging as versatile tools for CNS drug delivery, as they are biocompatible and biodegradable, penetrate biological membranes, encapsulate both hydrophobic and hydrophilic drugs, and also provide drug protection and controlled release [ 7 , 8 ]. In particular, poly(lactic co-glycolic acid) (PLGA) NPs and solid lipid nanoparticles (SLNs) have received considerable attention as drug delivery systems to the CNS [ 9 , 10 ].…”

Polymeric Metal Contrast Agents for T1-Weighted Magnetic Resonance Imaging of the Brain

“…Because polymers have high affinities for functionalization, polymeric NPs can be conjugated with targeting moieties that ensure brain internalization. − , In some cases, the polymer itself may even serve as the targeting moiety, like with the natural polymer, hyaluronic acid, which is recognized by LDLR receptors upregulated in the brain . Targeted brain delivery is an improvement upon the size-dependent diffusion into the brain, anyway, because it is more specific and less susceptible to premature clearance by the liver and kidneys. , Additionally, it makes polymeric CA NPs more widely applicable as they do not depend on the leakiness of the BBB for brain entry as traditional GBCAs do.…”

“…Still, too, simple polymer conjugation to achieve a coated CA is another approach that can be seen in recent literature. The advantages and disadvantages of each polymer-based delivery system have been reviewed extensively elsewhere. ,− …”

Functionalization strategies of polymeric nanoparticles for drug delivery in Alzheimer’s disease: Current trends and future perspectives

“…Notably, owing to their biocompatibility and chemical inertness, PS-NPs exhibits no short-term cytotoxicity in a cellular environment, and being easy to synthesize and functionalize in various sizes, they are believed to be a good model platform for investigating bio-nano interactions (Loos et al, 2014b). Chitosan deposition on NP surface can be conducted either via physicochemical adsorption or covalent bonding between the polymer functional groups (i.e., -NH 2 and -OH) and NPs (Annu et al, 2022). In a recent article, the potential of these two techniques has been described (Del Prado-Audelo et al, 2020).…”