A Reevaluation of Chitosan-Decorated Nanoparticles to Cross the Blood-Brain Barrier

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.

Evaluation of Antinociceptive Effects of Chitosan-Coated Liposomes Entrapping the Selective Kappa Opioid Receptor Agonist U50,488 in Mice

“…Because they have showed strong evidence for crossing the blood–brainbarrier [ 52 ], chitosan nanoparticles are studied for therapeutic compounds transportation as a potential therapy in Parkinson’s disease, Alzheimer’s disease, schizophrenia, gliomas, and cerebral ischemia [ 53 ].…”

Curcumin for parkinson´s disease: potential therapeutic effects, molecular mechanisms, and nanoformulations to enhance its efficacy

“…The loading of curcumin into these nanocarriers comprises numerous theoretical advantages, including increased solubility, enhancement of bioavailability, and improvement of stability (16). Moreover, depending on their formulation and surface functionalization, the nanoparticles would provide an increased ability to cross the BBB (41).…”

“…Nanoformulations intended to biomedical applications include polymeric nanoparticles, liposomes, lipid nanoparticles, solid lipid nanoparticles, and polymeric micelles. It should be noted that nanosystems for brain diseases generally exhibit sizes <200 nm to facilitate their crossing through the BBB with minimal risk (2,3,16,41). Likewise, these nanoparticles may be fabricated with innocuous and natural materials to produce biocompatible, biodegradable, and non-toxic drug delivery systems.…”

Insights into Terminal Sterilization Processes of Nanoparticles for Biomedical Applications

“…Likewise, nanoparticles may be loaded with diverse molecules by dissolution, entrapment, absorption, or encapsulation. Therefore, their applications may include drug delivery systems, gene therapy, tissue engineering, photodynamic cancer therapy, and contrast agents in imaging [ 3 , 4 , 5 , 6 ]. These applications need nanoparticles to exhibit biocompatibility, low toxicity, nonimmunogenicity, and sterility.…”