Recent expansions of novel strategies towards the drug targeting into the brain

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.

Keywords: BBB; brain; drug targeting; intranasal drug delivery; liposome; nanocarrier.

Figure 1

Schematic representation of drug transport across BBB via different mechanisms including passive diffusion (including paracellular transport of polar or hydrophilic drug and transcellular transport of lipidic or non-polar drug), receptor-mediated transport, ion channel transport of surface charged molecules, carrier-mediated transport of AA, glucose, larger proteins and peptides, and also the efflux transport that regulates the outflow of metabolites, drugs, toxins and neurotransmitters. Abbreviations: AA, amino acid; BBB, blood–brain barrier; BCECs, brain capillary endothelial cells.

Figure 2

Figure showing general structure of some important nanocarriers including liposome, polymeric nanoparticle, inorganic nanoparticle (iron oxide or magnetic nanoparticle and gold nanoparticle), nanogel, nanoemulsion, dendrimers and quantum dots used to target the therapeutic agents to the brain.