Overcoming blood–brain barrier transport: Advances in nanoparticle-based drug delivery strategies

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

“…The BBB is an exceptionally restrictive physical barrier that preserves the homeostasis of the brain tissue [25,26]. The surface area of the BBB is about 150 to 200 cm 2 per gram of brain tissue, constituting a gross area of 12 to 18 m 2 for an adult human being [2].…”

“…Other examples of physicochemical properties that can compromise the crossing of substances are ionization potential, pKa (ideal: low, between 7.5-10), molecular volume and flexibility (ideal: rotatable bonds fewer and in the range of less than 5), number of hydrogen bonds donors and acceptors (ideal: low, values in the range 1.5 and 2.12, respectively), partition coefficient, presence of charged system (ideal: basic compounds that in physiologic pH act as cationic moiety and interact with charged polar heads), polar surface area (ideal: low, between of 60-70) and protein binding (ideal: low, try to reduce the affinity for serum albumin) [2,31,32]. The BBB has shown a high selectivity that excludes more than 98% of therapeutic macromolecules and small molecules [26]. This selectivity is regulated by the presence of the Pglycoprotein, commonly referred to as the multidrug resistance protein [9].…”

“…One of these strategies is the usage of nanoparticulated systems such as polymeric nanoparticles [34], solid lipid nanoparticles [35], and silica nanoparticles [36], among others. The optimal performance of nanoparticles in drug release mainly depends on the size, zeta potential of the nanoparticle, surface The BBB has shown a high selectivity that excludes more than 98% of therapeutic macromolecules and small molecules [26]. This selectivity is regulated by the presence of the P-glycoprotein, commonly referred to as the multidrug resistance protein [9].…”

“…This selectivity is regulated by the presence of the P-glycoprotein, commonly referred to as the multidrug resistance protein [9]. This protein is capable of causing the drugs to return to the bloodstream through ATP-dependent efflux pumps, this event may be present even if the drug has already entered the BBB endothelium [26]. That phenomenon is frequently observed in the hydrophilic drugs or/and with high molecular weights.…”

“…Nanostructures such as polymeric nanocarriers, lipid nanoparticles, micelles, and inorganic nanoparticles have been proposed as drug carriers to treat different brain diseases due to their hydrophobic properties and high affinity for membrane lipids [26,81,82]. It is noteworthy that even though some of these nanosystems have reached brain tissue more efficiently compared to chitosan nanoparticles, their ability to cross the BBB has been enhanced by coating their surface with this polycation [59,[83][84][85].…”