Abstract
The blood-brain barrier (BBB) is a sophisticated and very selective dynamic interface composed of endothelial cells expressing enzymes, transport systems, and receptors that regulate the passage of nutrients, ions, oxygen, and other essential molecules to the brain, regulating its homeostasis. Moreover, the BBB performs a vital function in protecting the brain from pathogens and other dangerous agents in the blood circulation. Despite its crucial role, this barrier represents a difficult obstacle for the treatment of brain diseases because many therapeutic agents cannot cross it. Thus, different strategies based on nanoparticles have been explored in recent years. Concerning this, chitosan-decorated nanoparticles have demonstrated enormous potential for drug delivery across the BBB and treatment of Alzheimer’s disease, Parkinson’s disease, gliomas, cerebral ischemia, and schizophrenia. Our main objective was to highlight the high potential of chitosan adsorption to improve the penetrability through the BBB of nanoformulations for diseases of CNS. Therefore, we describe the BBB structure and function, as well as the routes of chitosan for crossing it. Moreover, we define the methods of decoration of nanoparticles with chitosan and provide numerous examples of their potential utilization in a variety of brain diseases. Lastly, we discuss future directions, mentioning the need for extensive characterization of proposed nanoformulations and clinical trials for evaluation of their efficacy.
Highlights
The brain is possibly the most sophisticated and evolved organ of human beings; protection of its function is a critical issue [1]
The chitosan addition is optimal when the carboxyl groups are still active to obtain covalent bonding. Transacylation reaction is another suitable approach, and it is more feasible on lipid-based nanoparticles because the ester groups present on lipidic molecules are available to react with the amino groups on the chitosan chains
Other reports described a significant difference regarding the effectiveness of solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) in brain targeting by the presence of the chitosan coating concerning non-coating ones
Summary
The brain is possibly the most sophisticated and evolved organ of human beings; protection of its function is a critical issue [1]. The main constituents of the BBB are microvascular endothelial cells, microglia, pericytes, and astrocytes, which help to maintain its selective permeability This feature allows the correct functioning of the synaptic and neuronal activity; the BBB performs a crucial role [3]. Despite the essential function of the BBB, it represents a formidable hurdle to efficient drug delivery to the brain and treatment of its diseases, making necessary the development of efficient drug delivery systems In this respect, diverse approaches have been proposed in recent years for the passage of drugs across the BBB, and nanoparticles have attracted significant attention for this purpose [8,9,10,11,12,13]. We discuss future directions, mentioning the need for extensive characterization of proposed nanoformulations and clinical trials for evaluation of their efficacy
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