Negatively charged albumins (NCAs, with the prototypes succinylated human serum albumin (Suc-HSA) and aconitylated human serum albumin (Aco-HSA)), modified proteins with a potent anti-human immunodeficiency virus type 1 (anti-HIV-1) activity in vitro, were studied for their pharmacokinetic behaviour in mice and their in vivo anti-HIV-1 efficacy in an HIV-1 infection model in mice. In contrast to the saturation kinetics found in rats, intravenous injections of 10-300 mg/kg for both NCAs showed a linear correlation between the area under the curve (AUC) and the dose. The elimination t( 1/4 ) was 25 and 30 min for Suc-HSA and Aco-HSA, respectively. Preinjections of an excess of formaldehyde-treated albumin (Form-HSA) resulted in plasma levels that were 3- and 4-fold higher for Aco-HSA and Suc-HSA, respectively. These data indicate that elimination is at least partly (scavenger) receptor-mediated. Organ distribution studies 10 min after injection showed an accumulation in liver (Suc-HSA 17.3 ± 6.6% of the dose; Aco-HSA 20.9 ± 2.3%) and lungs (Suc-HSA 12.7 ± 10.5%; Aco-HSA 16.0 ± 13.6). Intraperitoneal injection of 300 mg/kg Suc-HSA resulted in a final bioavailability of about 0.45. Suc-HSA was also evaluated for its in vivo neutralizing capacity in a human-to-mouse chimeric model for HIV-1 infection. Intraperitoneal injections of 300 and 3 mg/kg Suc-HSA, given 15-30 min before the mice were challenged with the virus, sufficed to protect these mice against infection with the HIV-1 III(B) strain.

Antiviral, Human immunodeficiency virus type 1, Negatively charged human serum albumins, Polyanion,
Antiviral Research
Department of Virology

Kuipers, M.E, Swart, P.J, Schutten, M, Smit, C, Proost, J.H, Osterhaus, A.D.M.E, & Meijer, D.K.F. (1997). Pharmacokinetics and anti-HIV-1 efficacy of negatively charged human serum albumins in mice. Antiviral Research, 33(2), 99–108. doi:10.1016/S0166-3542(96)01005-4