Larch arabinogalactan for hepatic drug delivery: isolation and characterization of a 9 kDa arabinogalactan fragment

Purified arabinogalactan [AG(37 kDa)] from Larix occidentalis is composed of repeating units of similar molecular weight and composition. A 9 kDa arabinogalactan [AG(9 kDa)] has been obtained in high yield from AG(37 kDa) either by autoclaving at 121°C or by exposure to alkaline solution in the presence of sodium borohydride. The weight average molecular weight of AG(37 kDa) was determined to be 37 and 38 kDa by intensity light scattering and sedimentation equilibrium, respectively. The weight average molecular weight of AG(9 kDa) was determined to be 9.1 and 9.5 kDa by intensity light scattering and sedimentation equilibrium, respectively. MALDI-TOF mass spectrometry yielded a molecular weight at the peak of the distribution of 8.3 kDa for AG(9 kDa). Both AG(37 kDa) and AG(9 kDa) exhibited narrow molecular-weight distributions (Mw/Mn ∼ 1.2). AG(37 kDa) and AG(9 kDa) exhibit nearly identical 13C-NMR spectra, monosaccharide composition, and sugar linkages. It is proposed that AG(37 kDa) is composed of covalently bound subunits of AG(9 kDa), AG(37 kDa) and AG(9 kDa) bind isolated hepatocyte asialoglycoprotein receptor equally well. As a result AG(9 kDa) is a candidate for use in hepatocyte directed drug delivery and may be more desirable for such use than is AG(37 kDa).