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Pharmaceutical Applications of Albumin
Published in Amit Kumar Nayak, Md Saquib Hasnain, Dilipkumar Pal, Natural Polymers for Pharmaceutical Applications, 2019
Albumin acts as a transporter for a broad range of endogenous substances like fatty acid, bilirubin, and exogenous ligands like penicillins, warfarin through reversible non-covalent association. Non-covalent Van Der Waals force or electronic interactions are responsible for this association. The drug of interest conjugates with a molecule which has a binding affinity for albumin. For examples, fatty acids can be conjugated to the drug of interest, which upon injection associates with albumin. This strategy has been specifically exploited in the development of Levemir® (Insulin detemir) for the treatment of diabetes. Levemir® contains an insulin analog with an exposed lysine residue that is conjugated to myristic acid (Klein et al., 2007; Hermansen et al., 2006; Home et al., 2006). Victoza® (Liraglutide) by Novo Nordisk is another diabetic drug which is a derivative of glucagon-like peptide-1 agonist (GLP-1) conjugated with a myristic acid at the ε-amino position of the N-terminal lysine. The drug after parenteral administration undergoes association with endogenous albumin in the blood through its fatty acid binding sites. Then drug slowly comes out of the association leading to enhancement of its half-life and bioavailability. Saturation of albumin with long Fatty Acid abolishes binding to FcRn receptor (Schmidt et al., 2013) which may be the limitations regarding half-life extension. Another example is “albutag” consisting of a small organic molecule, 4-(p-iodophenyl) butanoic acid derivatives that special affinity for albumin. The attachment of this tag to small molecules or recombinant proteins has been shown to be able to increase their half-lives. The tag has been conjugated to a free cysteine at the C-terminal end of a single-chain antibody (scFv) fragment with tumor specificity. That prolonged the half-life from ~20 min to 16.6 hours, in addition to improving tumor internalization (Trüssel et al., 2009).
Histological and immunohistochemical study of the effect of liraglutide in experimental model of non-alcoholic fatty liver disease
Published in Egyptian Journal of Basic and Applied Sciences, 2023
Mai Salah Nour, Zeinab Abd El-Hay Sakara, Nawal Awad Hasanin, Shereen Mohamed Hamed
Liraglutide is an analogue of glucagon-like peptide-1 (GLP-1) with 97% sequence similarity to human GLP-1. In 2010, liraglutide was accepted as a once-daily treatment for type 2 diabetes [9]. It is well recognized to reduce blood glucose levels by promoting glucose-dependent insulin secretion, lowering food intake and body weight and promoting beta-cell development [10].