Blood-brain barrier transport of cationized immunoglobulin G: Enhanced delivery compared to native protein

Journal Article · Thu Jun 01 04:00:00 EDT 1989 · Proc. Natl. Acad. Sci. USA; (United States)

DOI:https://doi.org/10.1073/pnas.86.12.4761· OSTI ID:5879199

Triguero, D; Buciak, J B; Yang, J; Pardridge, W M

IgG molecules are potential neuropharmaceuticals that may be used for therapeutic or diagnostic purposes. However, IgG molecules are excluded from entering brain, owing to a lack of transport of these plasma proteins through the brain capillary wall, or blood-brain barrier (BBB). The possibility of enhanced IgG delivery through the BBB by cationization of the proteins was explored in the present studies. Native bovine IgG molecules were cationized by covalent coupling of hexamethylenediamine and the isoelectric point was raised to greater than 10.7 based on isoelectric focusing studies. Native and cationized IgG molecules were radiolabeled with /sup 125/I and chloramine T. Cationized IgG, but not native IgG, was rapidly taken up by isolated bovine brain microvessels, which were used as an in vitro model system of the BBB. Cationized IgG binding was time and temperature dependent and was saturated by increasing concentrations of unlabeled cationized IgG (dissociation constant of the high-affinity binding site, 0.90 +/- 0.37 microM; Bmax, 1.4 +/- 0.4 nmol per mg of protein). In vivo studies documented enhanced brain uptake of 125I-labeled cationized IgG relative to (3H)albumin, and complete transcytosis of the 125I-labeled cationized IgG molecule through the BBB and into brain parenchyma was demonstrated by thaw-mount autoradiography of frozen sections of rat brain obtained after carotid arterial infusions of 125I-labeled cationized IgG. These studies demonstrate that cationization of IgG molecules greatly facilitates the transport of these plasma proteins through the BBB in vivo, and this process may provide a new strategy for IgG delivery through the BBB.

• Research Organization: Univ. of California, Los Angeles (USA)
• OSTI ID: 5879199
• Journal Information: Proc. Natl. Acad. Sci. USA; (United States), Journal Name: Proc. Natl. Acad. Sci. USA; (United States) Vol. 86:12; ISSN PNASA
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ALBUMINS
ANIMALS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOCHEMICAL REACTION KINETICS
BLOOD VESSELS
BLOOD-BRAIN BARRIER
BODY
BRAIN
CAPILLARIES
CARDIOVASCULAR SYSTEM
CATIONS
CATTLE
CENTRAL NERVOUS SYSTEM
CHARGED PARTICLES
DOMESTIC ANIMALS
GLOBULINS
HOURS LIVING RADIOISOTOPES
IMMUNOGLOBULINS
IN VITRO
INTERMEDIATE MASS NUCLEI
IODINE 132
IODINE ISOTOPES
IONS
ISOTOPES
KINETICS
LABELLED COMPOUNDS
MAMMALS
MEMBRANE TRANSPORT
NERVOUS SYSTEM
NUCLEI
ODD-ODD NUCLEI
ORGANIC COMPOUNDS
ORGANS
PERMEABILITY
PROTEINS
RADIOISOTOPES
RATS
REACTION KINETICS
RODENTS
RUMINANTS
SPECIFICITY
TEMPERATURE DEPENDENCE
TIME DEPENDENCE
TRITIUM COMPOUNDS
VERTEBRATES