PEG-conjugates

Tumor tissues overexpress matrix metalloproteinases (MMPs). A liposomal pDNA carrier (MEND) was developed containing PEG conjugated to lipid via a peptide linker that is a target sequence for MMPs. In this strategy, PEG is removed from the carrier via MMP-triggered cleavage [198]. Intravenous administration in... 

Kim SH, Jeong JH, Lee SH, Kim SW, Park TG (2006) PEG conjugated VEGF siRNA for anti-angiogenic gene therapy. J Control Release 116 123-129... 

Fig. 3 Chemistry of site-specific PEGylation developed by Brocchini et al. [5, 6]. After cleavage of the native disulfide bond between two cysteine thiols by reduction, the free cysteines are reacted with an a, (3-unsaturated PEG derivative to produce a PEG conjugate via a three-carbon bridge...

Scheme 2 Drug-PEG conjugate via a benzyl carbamate linkage and its thiolytic cleavage...

Hinds, K. and Kim, S. 2002. Effects of PEG conjugation on insulin properties. Advanced Drug Delivery Reviews 54(4), 505-530. 

Liu J, Ohta Si, Sonoda A, Yamada M, Yamamoto M, Nitta N, Murata K, Tabata Y (2007) Preparation of PEG-conjugated fullerene containing Gd3+ ions for photodynamic therapy. J. Controlled Rel. 117 104-110. 

Brain delivery of the anticancer drug daunomycin provides an example of the in vivo application of OX26-inununoliposomes [111]. Different formulations of [ H]-daunomycin were i.v. administered to rats either as the free drug or encapsulated in conventional liposomes, sterically-stabilized liposomes, or PEG-conjugated immunohposomes (Table 2.3). Plasma samples were taken at defined time points and after 1 h the animal was killed and drug concentrations in brain tissue were determined. 

Free daunomycin and not PEG-conjugated hposomes containing daunomycin, disappear rapidly from the circulation. Plasma clearance of the hposome was reduced 66-fold by PEG-conjugation. Coupling 29 0X26 monoclonal antibodies per PEG-liposome partially reversed the effect of PEG-conjugation on plasma clearance. 

Figure 8.4. Schematic diagram showing the structure of a typical polyethylene glycol (PEG) conjugate and the chemical structure of PEG-asparaginase.

Soluble polymer conjugates have been introduced into clinical practice in the last decade [90,94], Several PEG conjugates have been evaluated clinically [145] for cancer therapy including a PEG conjugate of asparaginase in the treatment of ALL in patients hypersensitive to the native enzyme [146], and a PEG conjugate of IL-2 [147],... 

Pegylated-L-asparaginase, PEG-conjugated L-asparaginase (of Escherichia coli) Erwinia L-asparginase is extracted from Erwinia chrysanthemi. 

The pulmonary delivery of rhG-CSF (18.8 kDa) and two PEG conjugates of rhG-CSF (PI, 81.5 kDa and P2, 146.8 kDa) was investigated in rats (Niven et al. 1994). Comparison of white blood cell responses after IT instillation of 500 pg/kg PI and P2 and rhG-CSF alone, demonstrated a greater response for more substituted PEG-rhG-CSF than rhG-CSF alone. The plasma concentration vs. time curve showed... 

Bolon B, Faust J, Storm N, et al. Cytoplasmic vacuoles in renal tubular epithelium of mice given polyethylene glycol (PEG)-conjugated proteins are reduced by alternating PEG size and conformation. Tox Sci 2001 60(1) 376. 

Fig. 11.3 PEG conjugation to the thiol group of cysteine yields stable thioesters, or disulfites that can be cleaved by free thiols.

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