Enhanced permeabilities of cationized‐bovine serum albumins at the blood‐nerve and blood‐brain barriers in awake rats

Abstract

Permeability-surface area products (PAs) of the blood-nerve barrier (BNB) and blood-brain barrier (BBB) to 125I-labeled native bovine serum albumin (nBSA, pI approximately 4), and to 2 cationized albumins (cBSA) of differing pI (pI approximately 8 and 11), were quantitatively determined in awake rats, using an i.v. bolus injection technique. Mean PAs of the BNB and BBB to 125I-nBSA, after a circulation time of up to 120 min, were (0.17 +/- 0.23) and (0.09 +/- 0.05) x 10(-5) ml/s.g. wet wt, respectively (n = 12 rats), and were not significantly different from 0 (P greater than 0.05). Mean PAs of the BNB and BBB to 125I-cBSA (pI approximately 8), after circulation time of 12 min, were (1.9 +/- 0.1) and (1.7 +/- 0.1) x 10(-5) ml/s.g wet wt, respectively (n = 8). Significant greater PAs, at both the BNB and BBB to 125I-cBSA (pI approximately 11) [(8.2 +/- 1.8) and (3.0 +/- 0.6) x 10(-5) ml/s.g wet wt, respectively (n = 12)], than both PA's of nBSA and cBSA (pI approximately 8) were found. The accumulation of 125I-cBSA in epi-perineurial tissues also was higher than that of 125I-nBSA, and was related to the degree of cationization. Our results indicate that, as at the BBB, the transfer of cationized serum albumin is enhanced over that of native albumin at the BNB of the mammalian peripheral nerve.

Effect of binding protein surface charge on palmitate uptake by hepatocyte suspensions

“…The effect of protein surface charge on the transcellular protein flux rate across endothelial cells (Smith & Borchardt, 1989), hepatocytes (Wall & Maack, 1985) and proximal tubular cells (Park & Maack, 1984) is well documented, as is its role in capillary permeability (Michel et al , 1985). Ghitescu et al (1992) and Wadhwani et al (1992) showed that protein surface charge is an important factor determining the membrane protein permeability properties. Charged groups at the membrane surface also have been shown to affect the activity of membrane‐bound enzymes by altering the local substrate and/or product concentration (Wojtczak et al , 1988).…”

“…Given the number of publications describing ionic interactions between cellular substrates and cell membranes, protein surface charge (pI) may be an important factor to consider when studying uptake processes. For example, cell membrane surface charge is known to affect the activity of membrane‐bound enzymes, protein‐membrane adsorption properties, transmembrane flux and capillary permeability properties of proteins (Norde & Lyklema, 1978; Park & Maack, 1984; Michel et al , 1985; Wojtczak et al , 1988; Smith & Borchardt, 1989; Ghitescu et al , 1992; Nishida et al , 1992; Wadhwani et al , 1992). Similarly, the surface charge of proteins affects their membrane adsorptive properties (Norde & Lyklema, 1978; Nishida et al , 1992).…”

Biopolymer albumin for diagnosis and in drug delivery

“…A typical example is the use of cationized proteins in brain delivery. It has been demonstrated that cationized albumin is able to traverse the capillary walls of isolated bovine brain capillaries [Kumagai et al, 1987] and penetrate the brain of the awake rat [Wadhwani et al, 1992].…”

Vascular permeability in the peripheral autonomic and somatic nervous systems: Controversial aspects and comparisons with the blood-brain barrier

“…Proteins such as albumin have been chemically modified to make them strongly basic ("cationized") or to give them additional carbohydrate groups ("glycated"). These modified proteins bind to and are transported across the otherwise impermeable endothelium Wadhwani et al, 1992). Some natural plasma proteins, notably transferrin (Pardridge et al, 1992;Rosenthal and Soothill, 1962) and insulin , enter the brain by receptor-mediated transport across endothelial cells.…”