Carboxylic groups, PEGylation

A number of PEGylation reactions with liposomes have been developed [66]. One of the methods utilizes lipophilic compounds that possess reactive groups such as amino and carboxyl groups. By incorporating these components into the bilayer membrane, 500-2,000 functional groups can be introduced onto the liposome... 

Fig. 11 Methods for the construction of PEGylated liposomes, (a) Liposomes possessing reactive groups, such as amino and carboxyl groups, can be prepared by incorporating lipophilic components containing these functional groups into a bilayer membrane. Functionalized liposomes can be PEGylated by reaction with activated PEG derivatives, (b) Preparation of PEGylated liposomes using PEG derivatives possessing lipid moieties...

An improvement in amine selective PEGylation chemistry came with the development of activated esters based on conversion of the mPEG terminal OH to a carboxyl group [39]. Esterification with N hydroxysuccinimide gave an activated ester that reacted readily with amines to give... 

The possibility of copolymerizing one or more macromonomers, synthesized as reported previously, along with the commercially available monomers characterized by the presence of hydrophilic groups such as PEGylated chains, carboxyl groups, quaternary ammonium salts, and sulfate groups, allows for the production of NPs through an emulsion polymerization without the use of any surfactants [12—14]. This feature is of extreme importance for applications in biomedical fields because surfactants are cytotoxic when injected into the bloodstream [15]. 

Kaminskas, L. M., Kelly, B. D., McLeod, V. M., Sbema, G., Boyd, B. J., Owen, D. J., et al. (2011). Capping methotrexate a-carboxyl groups enhances systemic exposure and retains the cytotoxicity of drug conjugated PEGylated polylysine dendrimers. Molecular Pharmaceutics, 8(2), 338-349. 

PEGylation at carboxylic groups with an amino PEG is not an easy procedure, since undesired cross-linking may occur between a protein s activated COOHs and a protein s amino groups, yielding a number of unwanted side products. 

PEGylation of -NH using activated carboxylic acid esters (Equation 3.3) is a well-developed strategy in bioconjugation technology. In these reactions, the polymer is connected to the activated carboxyl group by means of a linker, the nature of which can have a profound affect on the reactivity of the activated polymer and on the stability of the conjugate. 

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