Nanotherapeutics engineered to cross the blood-brain barrier for advanced drug delivery to the central nervous system

Abstract

Drug delivery to the brain remains challenging mainly due to the blood-brain barrier (BBB) that regulates the entrance of substances to the brain. Advances in nanotechnology have enabled the engineering of nanomedicines for biomedical applications including enhanced drug delivery into the brain. In this review, we describe strategies of nanomedicines engineered to traverse the BBB and deliver therapeutic molecules to target brain sites. We highlight the representative applications with materials including polymers, lipids, and inorganic elements for brain drug delivery. We finalize this review with the current challenges and future perspective of nanotherapeutics for advanced drug delivery to the brain.

Microengineered human blood–brain barrier platform for understanding nanoparticle transport mechanisms

“…To deliver drugs across this barrier, CNS delivery systems have been widely explored to cross the BBB 7 , including nanoparticle (NP)-mediated drug delivery with ligands specific to BBB endothelial surface receptors 8,9 . In particular, high-density lipoprotein (HDL)-mimetic NPs have been introduced as promising CNS delivery systems due to the innate endogenous character to facilitate the delivery of therapeutic molecules across the BBB via lipoprotein receptor-mediated transcytosis [10][11][12] .…”

Nanotechnology and Nanocarrier-Based Drug Delivery as the Potential Therapeutic Strategy for Glioblastoma Multiforme: An Update

“…To minimize unwanted interactions between nanomaterials and normal tissues, surface modification of nanoparticles with different molecules has been investigated for more than a decade [ 83 ]. Initially, polyethylene glycol (PEG) was used as a surface coating because of its hydrophilic external surface and inner hydrophobic polymeric matrix, which helps nanoparticles escape RES recognition and increases the half-life and persistence in the circulation [ 84 ]. In order to increase the affinity and specificity of nanoparticles for the targeted tissue, chitosan PEGylated albumin coated nanoparticles coupled with some antibodies were later developed for brain drug targeting through receptor-mediated transporter endocytosis [ 85 , 86 ].…”

“…During the last decade, various methods of liposomal formulations for the treatment of GBMs, novel conjugated agents, and receptor-mediated transcytosis have been investigated to facilitate their transport across the BBB [ 113 , 114 , 115 ]. For example, conjugation of polyethylene glycol (PEG) to the surface of a liposome phospholipid bilayer can extend the half-life of liposomes in the circulation because PEG can help the nanoparticles escape from the capture of RES [ 84 ].…”

Design and Development of Nanomaterial-Based Drug Carriers to Overcome the Blood–Brain Barrier by Using Different Transport Mechanisms

“…Synthetic and natural polymeric-based nanomaterials, such as hydroxyl polyamidoamine (PAMAM) [ 66 ], poly(D,L-lactide-co-glycolide) (PLGA) [ 67 ], and chitosan [ 68 ], illustrate their potential as drug carriers because of their high versatility in physical and chemical properties and adjustability in degradation. In addition, lipid-based NPs such as liposomes, with their amphiphilic phospholipid bilayer structure, have shown relatively low toxicity and a high drug-loading capacity [ 69 , 70 ]. Liposome NPs with the surface modified by transferrin, lactoferrin, glucose and glutathione polyethylene (PEG) [ 70 ] are proved to be effective strategies to increase the BBB permeability.…”