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Research Highlight: Degradable High Molecular Weight Monodisperse Dendritic Poly(ethylene glycols)

Bis-MPA dendritic scaffolds are used to create high mass (up to 66 kDa) monodisperse PEGylated dendrimers with a range of functional handles.

Poly(ethylene glycol) (PEG) is an attractive platform for a range of biomedical and pharmaceutical applications due to the low immunogenicity, antigenicity and toxicity. In particular, PEGylation of bioactive molecules is pursued in order to improve solubility in biological media and extend the circulation time after a drug is administered, thereby improving therapeutic outcomes. However, while well-defined, PEGs of higher molecular mass will have some extent of dispersity, existing as a distribution of molecular chains of different lengths. This heterogeneity compromises batch-to-batch consistency and can create issues for regulatory approval, QC and hinder clinical application.

In this research highlight, the authors use a combination monodisperse PEGs and flawless bis-MPA polyester dendrimers and dendrons to create biodegradable PEGylated dendrimers of the most precise structure and mass yet achieved, reaching masses comparable to large proteins such as bovine serum albumin.

The authors present a straightforward synthetic approach, using commercially available polyester dendrimers and monodisperse PEGs, to create a library of materials including those bearing fluorescent dyes and functional handles for further chemical attachment using click chemistry. The PEG-dendrimers were also found to be biocompatible with a range of cell lines, and fluorescent molecules could be tracked and showed to enter cells’ cytoplasm in a rapid manner. These exciting finds further confirm the potential of intricate polyester dendrimers as candidates for drug delivery and other key therapeutic targets.

Find the paper here.

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