A Facile, One-Pot, Surfactant-Free Nanoprecipitation Method for the Preparation of Nanogels from Polyglycerol–Drug Conjugates that Can Be Freely Assembled for Combination Therapy Applications

A well-established strategy to treat drug resistance is the use of multiple therapeutics. Polymer-based drug delivery systems (DDS) can facilitate a simultaneous delivery of two or more drugs. In this study, we developed and synthesized a dendritic polyglycerol (PG) nanogel (NG) system that allows for free combination of different fixed ratios of active compound conjugates within a single NG particle. As a proof of concept, we synthesized NGs bearing the chemotherapeutic agent doxorubicin (DOX) and paclitaxel (PTX) in different ratios, as well as conjugated dye molecules. Our combination PG NGs were formed by simply mixing PG–drug/dye conjugates bearing free thiol groups with PG-acrylate in an inverse surfactant-free nanoprecipitation method. With this method we obtained PG-NGs in the size range of 110–165 nm with low polydispersity indices. Solubility of hydrophobic PTX was improved without the need for additional solubilizing agents such as polyethylene glycol (PEG). Interestingly, we found that our NGs made from PG-DOX conjugates have a high quenching efficiency for DOX, which could be interesting for theranostic purposes.