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Coupling Computational and Experimental Techniques for the Design, Characterization, and Performance of Self-Assembled Dendrimers for Heparin and DNA Binding
Published in Costas Demetzos, Stergios Pispas, Natassa Pippa, Drug Delivery Nanosystems, 2019
Domenico Marson, Erik Laurini, Maurizio Fermeglia, Sabrina Pricl
To ensure the optimal level of heparin as an anticoagulant during medical operations, the quantification of this polyanion in blood is of paramount importance. In current practice, this is typically achieved via activated clotting time assays [2]. These measurements, however, suffer from several drawbacks, including (i) difficulty in determining the exact value of heparin levels, (ii) the amount of time required to complete the assays, and (iii) the impossibility of these tests to be carried out on a patient in a simple manner in situ. Moreover, once a surgical procedure in which heparin was used is concluded, there is an immediate need to neutralize its anticoagulant effect and allow blood clotting and recovery to begin. At the time being, the only Food and Drug Administration (FDA)-approved heparin antidote is protamine sulfate, a small, arginine-rich protein of shellfish origin. Protamine acts as a heparin neutralizer by forming a supermolecular complex (Fig. 8.1) driven by electrostatic interactions between the cationic arginine groups and the anionic heparin [3]. However, the binding is not selective for active or inactive heparin sequences. Furthermore, and most importantly, protamine can cause significant adverse effects, with major complications arising in 2.6% of cardiac surgeries, while up to 10% of patients treated with this protein experience different sorts of problems [4].
Drug-induced bronchospasm
Published in Philippe Camus, Edward C Rosenow, Drug-induced and Iatrogenic Respiratory Disease, 2010
K Suresh Babu, Jaymin Morjaria
Reactions to insulin therapy have occurred since the launch of animal insulin in 1922. With the initiation of recombinant human insulin, however, the incidence of insulin-induced allergic reactions has decreased. Anaphylactic reactions have been reported, though are rare, and IgE antibodies have been demonstrated,41 sometimes causing acute pulmonary hypertension. Reactions to protamine-containing insulins may be caused by the protamine component in the insulin preparation and not the insulin itself. Protamine sulphate is a low-molecular-weight polycationic protein that is used to reverse the anticoagulant properties of heparin, and it is also complexed to insulin to delay absorption. Dykewicz et al. reported on two patients with diabetes who had anaphylaxis in response to neutral protamine Hagedorn insulin and to protamine, indicating that protamine-specific IgE antibodies were responsible for the anaphylactic reactions.42 Inhaled insulin (Exubera), initially approved for the management of diabetes and then withdrawn from the market, had respiratory adverse events reported in approximately 11.6 per cent.43 It is not entirely certain, but the reactions might be due to the increased immunogenicity of inhaled insulin arising from the structural changes in insulin during manufacture of the powder, or due to differences in immune responses related to different routes of drug delivery, storage conditions, or pre-sensitization with subcutaneous insulin used previously; and pulmonary insulin may have an increased antibody response. This suggests that site of delivery and susceptibility of the recipient may significantly affect immune responses.44,45
LyP-1-conjugated Fe3O4 nanoparticles suppress tumor growth by magnetic induction hyperthermia
Published in Journal of Biomaterials Science, Polymer Edition, 2018
Peishan Teo, Xiaowen Wang, Jieying Zhang, Han Zhang, Xin Yang, Yun Huang, Jintian Tang
Our previous studies have shown that SPIONs with amphipathic polymer pullulan acetate, 3-aminopropyltriethoxysilane and protamine sulfate-modified surface worked well on other cancer cells in vitro by MIH [19–22]. Many other reports found that other molecules (e.g. folate, chitosan, and 3-aminopropyltriethoxysilane, etc.) coated SPIONs have satisfying properties in biocompatibility, targeted drug delivery, and thermal capability [3,4,19,21–23]. In the present study, the polyethylene glycol (PEG)-SPIONs and LyP-1-SPIONs accumulated in the human breast cancer and colon cancer cell lines, MCF-7 and CT-26. We compared the effects of PEG-SPIONs and LyP-1-SPIONs on tumor size suppression by combined MIH and targeted therapy in vitro.