Targeting of AIDS related encephalopathy using phenylalanine anchored lipidic nanocarrier

Disturbed Amino Acid Metabolism in HIV: Association with Neuropsychiatric Symptoms

“…In a recent study in Wistar rats, facilitated transport of efavirenz (a non-nucleoside reverse transcriptase inhibitor) across the blood–brain barrier using phenylalanine-anchored solid lipid nanoparticles was shown to improve bioavailability and maintain therapeutic levels in the brain for an extended period of time, probably enabling a significant eradication of the viral load ( 124 ).…”

Biotin and Glutathione Targeting of Solid Nanoparticles to Cross Human Brain Endothelial Cells

“…Glucose analog-targeted vesicular NPs were used successfully to deliver vasoactive intestinal peptide to brain in mice [14]. Phenylalanine, a ligand of the large amino acid transporter-1 (LAT-1, SLC7A5), used as a vector to target solid lipid NPs increased the transfer of the anti-HIV agent efavirenz across a BBB model in vitro and the drug's penetration to the brain of rats [15]. A delivery system based on dendrigraft containing doxorubicin and targeted by a choline-derivate with high affinity to choline transporter (SLC44A1) was more cytotoxic to glioma cells both in vitro and in vivo than non-targeted NPs or doxorubicin alone [16].…”

Lipid Nanocarriers for Anti-HIV Therapeutics: a Focus on Physicochemical Properties and Biotechnological Advances

“…Aside from extending the circulation time of nanocarriers, it is also critical to use targeting strategies that can deliver ARV drugs to sites of latent HIV reservoirs such as lymph nodes, the spleen, and the gut mucosa, where HIV-target cells such as memory CD4+ T cells, macrophages, microglia, and astrocytes in the CNS are prevalent [148]. Some of these targeting strategies include: (i) surface functionalization of nanocarriers with sugar molecules like mannose [13,102] or galactose [14,15,99] that are recognized by lectin receptors found on the surface of cells from the mononuclear phagocyte system (MPS); (ii) coating of nanocarriers with hydrophilic molecules (e.g., aminoacids, glucose) to facilitate BBB permeation by carrier mediated transcytosis [55]; (iii) engineering of the lipid matrix of the nanocarriers (SLN, NLC, nanoemulsions) in order to mimic low density lipoproteins (LDL) that are recognized by LDL receptors, thus facilitating BBB permeation by receptor mediated transcytosis [54,55,64,65,85,87,89,90,128]; (iv) functionalization with ligands (e.g., HSA and monoclonal antibody (mAb)) that enhance BBB permeation by receptor mediated transcytosis [65,128]; (v) inhibition of Pgp, which increases brain specific accumulation [89]; and (vi) magnetic aided transport across BBB [121] and to MPS cells [122].…”