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Binding of memantine to melanin: influence of type of melanin and characteristics

Koeberle, M. and Hughes, P.M. and Skellern, G.G. and Wilson, C.G. (2003) Binding of memantine to melanin: influence of type of melanin and characteristics. Pharmaceutical Research, 20 (10). pp. 1702-1709. ISSN 0724-8741

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The objectives of this study were to characterize sepia, synthetic, and bovine melanin and to determine their binding characteristics to the drug memantine. Physical methods were used to characterize sepia, synthetic, and bovine melanin. Their binding properties toward memantine were determined in deionized water and phosphate-buffered saline (PBS) at 37°C. Melanin-memantine binding was measured indirectly by determining the unbound fraction of memantine. Curve fitting according to the Langmuir binding isotherm for one binding site was used for the determination of binding capacity (B Lmax ) and dissociation constant (K D ). Synthetic and sepia melanin had comparable Gaussian particle size distributions, whereas bovine melanin showed a heterogeneous distribution profile. The suspension medium had a small effect on the particle size distribution of synthetic and bovine melanin. There were characteristic differences in the infrared spectra of the melanins. The rank order for B Lmax in deionized water was sepia > bovine > synthetic melanin. However, when the melanins were suspended in PBS, the B Lmax values were lower, and the rank order was bovine > sepia > synthetic. Whereas the K D values for sepia and synthetic melanin remained largely the same in deionized water and PBS, the K D value for bovine melanin in PBS was more than twice than in deionized water. This study showed that the physical characteristics of the melanins investigated differ markedly. The binding of memantine to melanin is thought to be determined by the different chemistries of the melanins, particle size, and buffer electrolytes.