Protein HESylation for half-life extension: Synthesis, characterization and pharmacokinetics of HESylated anakinra

Drug Delivery Systems Based on Hydroxyethyl Starch

“…It has been approved for rheumatic arthritis and recommended for patients with an insufficient response to other anti-rheumatic drugs. 40,41 It has to be 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 administrated at a daily dose of 100 mg, which is apparently, inconvenient and costly.…”

Nanoparticles from renewable polymers

“…Hydroxy ethyl starch (HES) based on natural starch, which is modified with ethylene glycol units, has proven to exhibit a stealth effect similar to PEG (see below, polyesters). The reduced protein adsorption of HES was already proven by several pharmaceuticals that are modified with it (Noga et al, 2012; Liebner et al, 2014). As a typical cross-linker for polysaccharides in early reports glutaraldehyde was frequently applied, e.g., for chitosan-based nanoparticles (Zhi et al, 2005), however the toxicity of glutaraldehyde limits its application in drug delivery as residues are difficult to remove from the crosslinked particles but may leak out during application.…”

“…To overcome this problem many particles are modified with poly(ethylene glycol) (PEG), which reduces the amount of adsorbed protein due to the so called “stealth effect,” which increases blood half life time by several orders of magnitude. The so called “PEGylation” is well-known for nanoparticles or molecularly dissolved drugs as the highly hydrated polyether reduces protein adsorption dramatically, (Bazile et al, 1995; Torchilin and Trubetskoy, 1995; Peracchia et al, 1999a,b; Andrieux and Couvreur, 2009) however, PEG is not degraded in vivo making a search for degradable alternatives in combination with degradable drug carriers necessary (Liebner et al, 2014) (see polysaccharides). Encapsulated material can either be released by diffusion from the polymeric matrix of the nanoparticles, and seems to depend on several factors as the preparation conditions, and the solubility of the drug in the dispersion medium.…”

Identification of mangiferin as a potential Glucokinase activator by structure-based virtual ligand screening

“…The recombinant GK protein was labeled with Monolith NTTM Protein Labeling Kit RED (Cat#L001) according to the kit instructions2829. Labelled GK concentration was adjusted to 200 nM.…”