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Absorptive-Mediated Transcytosis

AMT can facilitate drug transport across the BBB through cationic proteins or cell- penetrating peptides (CPPs) [68]. The mechanism is primarily based on electrostatic interactions between positively charged protein moieties and negatively charged brain endothelial cells. For example, cationic bovine serum albumin—conjugated PEGylated nanoparticles (CBSA-NP) exhibited 7.76 times higher permeability relative to plain BSA-NP across BBB [69]. Similarly, aclarubicin (ACL)-loaded bovine serum albumin—conjugated PEGylated nanoparticles (CBSA-NP-ACL) exhibited prolonged survival of a glioblastoma-bearing mice [70].

Furthermore, CPP-based drug delivery systems have shown potential in enhanced BBB transport. Delivery ofcargoes including peptides, proteins, DNA/RNA, antibodies, imaging agents, and nanodrug carriers such as liposomes and micelles has become possible by overcoming lipophilic barriers of cellular membrane with CPPs. These peptides are typically a chain of cationic amino acids such as lysine or arginine or sequences containing polar/charged and nonpolar, hydrophobic amino acids in an alternating pattern [71]. CPPs are derived from natural proteins including TAT, penetratin, and the Syn-B vectors. Among these, TAT is the most frequently used. Several studies have shown the potential of TAT-modified nanodrug carrier transport into the brain for diagnosis and treatment ofCNS disorders. For instance, TAT (AYGRKKRRQRRR) was covalently conjugated with cholesterol to prepare doxorubicin-loaded liposomes for glioma therapy. Higher brain concentrations of doxorubicin were achieved resulting in higher survival rates of glioma-bearing rats. These studies show that AMT can be utilized as a potential strategy for targeting BBB [72].

 
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