PEGylation releasable

Although the detailed mechanism of the longer circulation time of branched PEGylated protein is unclear, the architecture of PEG affects the release profile, the pharmacokinetics of the chug [29], and the behavior of the protein at the interface (e.g., protein absorption on hydrophobic surfaces [30]). 

ProLynx LLC has developed another type of releasable PEGylation technology based on the p-elimination reaction shown in Scheme 4. In this system, the release rate of the native drug is determined by the acidity of the proton adjacent to the... 

Scheme 3 Releasable PEGylation based on 1,6-benzyl elimination prodrug strategy...

Scheme 4 Releasable PEGylation based on the (3-elimination reaction...

Fig. 9 Utility of de-PEGylation technology in liposomes, (a) PEG derivative possessing a lipid moiety. The covalent bond between PEG and the lipid moiety can be cleaved by stimuli such as those within the acid environment of cancer and inflammation, (b) After binding the target cell via specific recognition of the receptor by the ligand, PEG molecules on the surface of the liposome are cleaved. The release of PEG facilitates membrane fusion of the liposome and liposome decomposition, resulting in efficient drug delivery...

Peleg-Shulman T, Tsubery H, Mironchik M, Fridkin M, Schreiber G, Shechter Y (2004) Reversible PEGylation a novel technology to release native interferon alpha2 over a prolonged time period. J Med Chem 47 4897 1904... 

Filpula D, Zhao H (2008) Releasable PEGylation of proteins with customized linkers. Adv Drug Deliv Rev 60 29 19... 

Peracchia MT, Fattal E, Desmaele D, Besnard M, Noel JP, Gomis JM, Appel M, d Angelo J, Couvreur P (1999) Stealth PEGylated polycyanoacrylate nanoparticles for intravenous administration and splenic targeting. J Control Release 60 121-128. 

Interferon is the approved treatment for hepatitis C. In general, there are four different treatments (1) IFN-a, (2) combination therapy of IFN-a and another drug called ribavirin, (3) pegylated IFN-a, and (4) pegylated IFN-a with ribavirin. Pegylated interferon contains polyethylene glycol, which increases the half-Ufe (see Section 5.3.5) from 6 hours to 45 hours and slows down the body s absorption of interferon. In this way, a more controlled release of interferon is achieved to prolong absorption. Instead of a subcutaneous injection of three times weekly, the frequency can be reduced to once weekly. 

Charrois GJ, Allen TM. Drug release rate influences the pharmacokinetics, biodistribution, therapeutic activity, and toxicity of pegylated liposomal doxorubicin formulations in murine breast cancer. Biochim Biophys Acta 2004 1663(1-2) 167. 

Kozlowski, A., and J.M. Harris, Improvements in protein pegyylation pegylated interferons for treatment of hepatitis C. J Controlled Release, 2001. 72 217-224. 

Filbey JA, Charles SA. Shellac to PEGylation 2500 years of polymers in controlled release drug delivery. Drug Delivery Tech 2005 5(6) 64—69. 

Mannisto M, Vanderkerken S, Toncheva V et al (2002) Structure-activity relationships of poly(L-lysines) effects of pegylation and molecular shape on physicochemical and biological properties in gene delivery. J Control Release 83(1) 169—182... 

A receptor-mediated gene delivery system using streptavidin and biotin-derivatized, pegylated epidermal growth factor. /. Control. Release 83 109-119. 

P. G. Schmidt. 2005. PEGylated insulin in PLGA microparticles. In vivo and in vitro analysis./. Control. Release 104 447-460. 

Garinot, M., V. Fievez, et al. (2007). PEGylated PLGA-based nanoparticles targeting M cells for oral vaccination. J Control Release 120(3) 195-204. 

Prego, C., D. Torres, et al. (2006). Chitosan-PEG nanocapsules as new carriers for oral peptide delivery. Effect of chitosan pegylation degree. J Control Release 111(3) 299-308. 

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