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Molecular Aspects of Anti-Polysaccharide Antibody Responses
Published in Maurizio Zanetti, J. Donald Capra, The Antibodies, 2002
Kurt Brorson, Pablo Garcia-Ojeda, Kathryn E. Stein
Dextrans, exo-polysaccharide polymers of glucose produced by Leuconostoc mesenteroides bacteria, have been used as synthetic blood volume expanders [81]. Anti-dextran antibodies are clinically important because pre-existing anti-dextran antibodies, particularly antibodies reactive with non-a(1: 6) linkage dextran, correlate with anaphylactic reactions in patients given synthetic blood volume expanders. Dozens of strain specific dextrans exist, which differ in the relative proportion of a(1: 2), a(1: 3), a(1: 4), or a(1: 6) linkages. Two dextrans, B512F and B1355S, have been extensively characterized immunologically. B512F dextran contains mostly a(1: 6) linkages (90%) with 5% a(1: 3) branch linkages and 5% (1:) non-reducing end groups. B1355S dextran contains a high proportion of a(1: 3)-a(1: 6) linear repeating linkages, with 10% a(1: 3) branch linkages and 10% a(1:) non-reducing end groups. Because of their divergent linkage structures, antibody responses against both dextrans differ in VH:VL usage. Synthetic polyglucans and nigerose, a poly-a(1: 3) glucose isolated from Aspergillus niger, are available for fine specificity analysis and to examine binding to pure a(1: 3) linkages.
Cyclodextrin-based nanosponges as promising carriers for active agents
Published in Expert Opinion on Drug Delivery, 2019
Saeideh Allahyari, Francesco Trotta, Hadi Valizadeh, Mitra Jelvehgari, Parvin Zakeri-Milani
Doxorubicin (Adriamycin®) [70] as a hydrophilic drug (aqueous solubility 10 mg/ml) [10,50] and one of the most widely used anticancer agents, acts as DNA synthesis inhibitor in cancer cells. Doxorubicin normally is released very slowly at pH = 1.2 (about 1% after 120 min), but in the case of CDNSs, its release rate was enhanced with increasing in pH value (about 29% after 3 h at pH 7.4) [2,13]. This study revealed that the novel complex formulation can guarantee the main release of doxorubicin in intestinal region to protect it from gastric environment. In another study about doxorubicin, Caldera et al. modified CDNSs not only to provide a slow release of doxorubicin in tumor environment in loco-regional treatment but also increase its incorporation into carrier. Through this modification, in place of CDs, a new type of cyclic oligosaccharide, cyclic nigerosyl-1–6-nigerose (CNN), was used as a quiet polar building block because of its hydroxyl groups arrangement [50,71]. They used pyromellitic dianhydride as a cross-linking agent for the production of CNN NSs. They revealed that doxorubicin encapsulation efficiency was about 95% and slow drug release at pH 7.4 (20% drug release after 14 days and reaching 32.5% after 21 days) was shown. Finally, they demonstrated this novel NS as a favorable carrier for tumor local treatment [50]. Biofunctionalization of CDNSs is also another modification of this carrier that is used for improving delivery characteristic of it. Therefore researchers selected doxorubicin as a model drug in studying the functionalization of this carrier with cholesterol. They proved that according to images by laser scanning confocal microscopy, this biomolecule can improve the interaction property of CDNSs with cells and receptors and enhance cellular uptake of drug [51]. These studies show novel strategies and attractive ideas for improving CDNSs’ effect on solubility and bioavailability of drug molecules.