<p>Recent expansions of novel strategies towards the drug targeting into the brain</p>

Abstract

The treatment of central nervous system (CNS) disorders always remains a challenge for the researchers. The presence of various physiological barriers, primarily the blood–brain barrier (BBB) limits the accessibility of the brain and hinders the efficacy of various drug therapies. Hence, drug targeting to the brain, particularly to the diseased cells by circumventing the physiological barriers is essential to develop a promising therapy for the treatment of brain disorders. Presently, the investigations emphasize the role of different nanocarrier systems or surface modified target specific novel carrier system to improve the efficiency and reduce the side effects of the brain therapeutics. Such approaches supposed to circumvent the BBB or have the ability to cross the barrier function and thus increases the drug concentration in the brain. Although the efficacy of novel carrier system depends upon various physiological factors like active efflux transport, protein corona of the brain, stability, and toxicity of the nanocarrier, physicochemical properties, patient-related factors and many more. Hence, to develop a promising carrier system, it is essential to understand the physiology of the brain and BBB and also the other associated factors. Along with this, some alternative route like direct nose-to-brain drug delivery can also offer a better means to access the brain without exposure of the BBB. In this review, we have discussed the role of various physiological barriers including the BBB and blood-cerebrospinal fluid barrier (BCSFB) on the drug therapy and the mechanism of drug transport across the BBB. Further, we discussed different novel strategies for brain targeting of drug including, polymeric nanoparticles, lipidic nanoparticles, inorganic nanoparticles, liposomes, nanogels, nanoemulsions, dendrimers, quantum dots, etc. along with the intranasal drug delivery to the brain. We have also illustrated various factors affecting the drug targeting efficiency of the developed novel carrier system.

Pharmacotechnical Development of a Nasal Drug Delivery Composite Nanosystem Intended for Alzheimer’s Disease Treatment

“…While preventing the neurotoxic xenobiotics' access into the central nervous system (CNS) to protect it, it also strongly limits the administration of neuroprotective drugs to the CNS. The direct nose-to-brain delivery has appeared as a non-invasive powerful strategy to deliver drugs to the brain bypassing the BBB [6]. The most important direct pathway to the brain is the transport or the diffusion directly to the brain through the olfactory mucosa pathway in the olfactory region [7].…”

Breaking Barriers: Bioinspired Strategies for Targeted Neuronal Delivery to the Central Nervous System

“…Despite all the great advantages related to these vectors, there are some features limiting their applicability to some extent, such as low solubility, poor stability and low encapsulation efficiency, which still need to be overcome [34,55].…”

Advances of Nano-Structured Extended-Release Local Anesthetics

“…Further researches and design manufacturing are needed to confirm and maximize this benefit. Liposomes have been used in brain-directed drug delivery due to good biocompatibility and lipophilicity [57,58]. There are several mechanisms mediating penetration through BBB.…”

“…When liposomes are small enough, such as unilamellar liposomes encompassing lipophilic drugs, passive diffusion may occur. Modifications are also designed to strengthen ligand-receptor binding to facilitate brain-directed drug delivery [57]. Therefore, reverse designs such as negative net charge and lack of BBBspecific ligand can help prevent brain penetration and enhance safety.…”