Delivery of peptides and proteins through the blood-brain barrier

Nanomedicine in the diagnosis and therapy of neurodegenerative disorders

“…Protein conjugations with wheatgerm agglutinin [95,96] or cationic moieties ("cationization") [316][317][318] were shown to enhance CNS delivery of these proteins through adsorptive endocytosis. However, toxicity and antigenicity of such modified proteins restricts their medical use [319]. Alternatively, protein conjugates with antibodies to insulin or transferrin receptors were also considered [319][320][321][322].…”

“…However, toxicity and antigenicity of such modified proteins restricts their medical use [319]. Alternatively, protein conjugates with antibodies to insulin or transferrin receptors were also considered [319][320][321][322]. For example, basic fibroblast growth factor and brain-derived neurotrophic factor each were conjugated with OX26 antibody, resulting in an increased entry of these proteins to the brain and an increased neuroprotective effects in cerebral trauma models [323][324][325].…”

Microenvironmental regulation of biomacromolecular therapies

“…Various recombinant growth factors and antibodies are being used to elicit specific cellular activities that are useful for wound healing and regeneration of tissues and organs, or to limit the pathogenesis and metastasis of malignant cells (reviewed elsewhere) [1][2][3][4][5] . Different growth factors may also be combined to attain synergistic improvements in therapeutic efficiency 52,53 .…”

“…A broad array of therapeutic biomacromolecules including proteins [1][2][3][4][5] , plasmid DNAs (pDNAs) 6 and various forms of RNA have been identified 7,8 , engineered and used in various clinical trials and approved products 9,10 . The completion of the Human Genome Project will probably accelerate the discovery and application of biomacromolecular therapies.…”

Development of neuropeptide drugs that cross the blood-brain barrier

“…A number of strategies have been used to enhance the stability and thus the bioavailability of this peptide, including cyclization, 12,39 halogenation, 40 methylation, 41,42 and cationization. 43,44 The met-enkephalin analog, DPDPE, is a cyclized peptide containing D-penicillamine (D-Pen) at positions 2 and 5. 45,46 The two D-Pens, form a disulfide bridge that conformationally constrains the peptide, leading to increased metabolic stability (T 1/2 Ͼ 500 min), bioavailability, and BBB permeability.…”