Modulation of electrostatic interactions to improve controlled drug delivery from nanogels

- The design of nanogels as drug delivery systems based on electrostatic interaction among drug and polymers is proposed.
- Nanogels can be synthetized tuning their positive charge density, according to the protonation of PEI at different pH.
- No biorthogonal chemistry strategies are applied to the polymers or drugs.
- Drug release is efficiently modulated by charge density of PEI chains.
- The effect of counterion on nanogel synthesis is investigated and allows controlling the drug release.

The synthesis of nanogels as devices capable to maintain the drug level within a desired range for a long and sustained period of time is a leading strategy in controlled drug delivery. However, with respect to the good results obtained with antibodies and peptides there are a lot of problems related to the quick and uncontrolled diffusion of small hydrophilic molecules through polymeric network pores. For these reasons research community is pointing toward the use of click strategies to reduce release rates of the linked drugs to the polymer chains. Here we propose an alternative method that considers the electrostatic interactions between polymeric chains and drugs to tune the release kinetics from nanogel network. The main advantage of these systems lies in the fact that the carried drugs are not modified and no chemical reactions take place during their loading and release. In this work we synthesized PEG-PEI based nanogels with different protonation degrees and the release kinetics with charged and uncharged drug mimetics (sodium fluorescein, SF, and rhodamine B, RhB) were studied. Moreover, also the effect of counterion used to induce protonation was taken into account in order to build a tunable drug delivery system able to provide multiple release rates with the same device.

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