LAUSR

The interaction of intravenous immunoglobulin and three camptothecin analogs, including topotecan, 10-hydroxycamptothecin, 7-ethyl-10-hydroxycamptothecin (SN-38), was studied respectively in vitro. The bindings of intravenous immunoglobulin to these camptothecins were characterized by 2 and/or 4 binding sites with the average affinity constants Ko of 103 ~ 104 M−1 at pH 4.0 and 289 ~ 310 K, which were spontaneous, non-specific and weak drug–protein interactions. The observed Fourier transform infrared spectra of intravenous immunoglobulin indicated a partial unfolding of the typical β structure of protein after addition of camptothecins. Based on their distinctive UV–Vis spectra between solutions at pH 4.0, 7.40, and 10.0, the lactone-carboxylate equilibrium of 8.0 μM analogs in pH 7.40 PBS at 310 K in the absence and presence of 2.0 μM intravenous immunoglobulin shifted to the right with the lactone-to-total ratios decreasing from 34.47, 86.68, and 90.40% to 29.76 ~ 32.71%, 56.56 ~ 68.58%, and 86.47 ~ 87.35% for topotecan, 10-hydroxycamptothecin and SN-38, respectively. However, intravenous immunoglobulin could maintain higher circulatory levels of the biologically active species at physiological pH 7.40 in contrast to human serum albumin. Molecular docking was used to calculate the interaction mode and the hydrogen bonding formations were observed between camptothecins and residues of immunoglobulin G. Intravenous immunoglobulin would serve as a transport protein (carrier) for camptothecins.