Stabilization PEGylation

Y. S. Youn, J.Y Jung, S.H. Oh, S.D. Yoo, K.C Lee, Improved intestinal delivery of salmon calcitonin by Lysl8-amine specific PEGylation stability, permeability, pharmacokinetic behavior and in vivo hypocalcemic efficacy. /, Control. Release, 114 (3) 334-342,2006. 

Interestingly, this behavior of the reaction mixture can be prevented by employing another principle of particle stabilization steric protection. Inclusion of pegylated comonomer (PEG-AEPD) into the reaction mixture did enable the formation of nonaggregating DNA particles. It also caused the particles to form worm -like structures (as judged by transmission electron microscopy) that have previously been observed with DNA complexes formed from block copolymers of PEL and PEG [98]. 

Neutropenia associated with interferon or pegylated interferon therapy is defined as an absolute neutrophil count (ANC) of less than 1000 cells/mm3 in rare cases, an ANC less than 500 cells/mm3 maybe observed. The neutropenia is more common and in some cases more severe with pegylated interferon than with unmodified interferon. Neutropenia usually occurs within the first 2 weeks after initiating either formulation of interferon, with the WBC count stabilizing by week four or six. The neutropenia is reversible upon discontinuing therapy. Granulocyte colony-stimulating factor has been used as an adjunctive therapy for interferon-induced neutropenia in hepatitis patients.44... 

Tamura A, Oishi M, Nagasaki Y (2009) Enhanced cytoplasmic delivery of siRNA using a stabilized polyion complex based on PEGylated nanogels with a cross-linked polyamine structure. Biomacromolecules 10 1818-1827... 

Merdan T, Kunath K, Petersen H, Bakowsky U, Voigt KH, Kopecek J, Kissel T (2005) PEGylation of poly(ethylene imine) affects stability of complexes with plasmid DNA under in vivo conditions in a dose-dependent manner after intravenous injection into mice. Bioconjug Chem 16 785-792... 

PEG is a widely used molecule as a component in pharmaceutical formulations. PEG is particularly useful thanks to its low cost and various simple synthetic methods (26). PEG-lipid has been developed as a means of stabilizing conventional liposomes. A lipid moiety has been linked to the large PEGylated head in order to anchor the molecule to the particles. Instead of shielding a direct layer of polymer PEG around the particle, which would be less stable, the idea is to favor hydrophobic interactions between the PEG-lipid and the particle bilayer lipids. This anchor had led to two conformations of the PEG on the particle surface commonly called mushroom and brush regimes (27), representing a more condensed or extended conformations... 

As expected, acid-labile PEG did not increase the circulation time of the lipoplexes as compared to PEGylated lipoplexes but allowed for the same level to be reached, indicating the stability of the acid-sensitive PEG-lipid moiety in the blood. 

These polymers have been designed to achieve serum stability and sustained circulation with the PEGylated peptide, specific targeting to hepatocytes with... 

Salhanick AI, Clairmont KB, Buckholz TM, Pellegrino CM, Ha S, Lumb KJ (2005) Contribution of site-specific PEGylation to the dipeptidyl peptidase IV stability of glucose-dependent insulinotropic polypeptide. Bioorg Med Chem Lett 15 4114-4117 Sanderink G-J, Artur Y, Siest G (1988) Human aminopeptidase a review of the literature. J Clin Chem Clin Biochem 26 795-807... 

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