Concentration of polymer nanoparticles through dialysis: Efficacy and comparison with lyophilization for PEGylated and zwitterionic systems.
2020
Abstract Biodegradable polymeric nanoparticles (NPs) are attracting increasing attention as carriers for drug delivery. However, one of the main factors limiting their transition to the market is their premature degradation and release of the payload during the storage. Therefore, for increasing the formulation shelf-life, the removal of water is of paramount importance. In this work, we synthesized both polyethylene glycol (PEG)-stabilized and zwitterionic NPs via Reversible Addition Fragmentation Chain Transfer (RAFT) Polymerization. We demonstrated that lyophilization leads the PEGylated NPs to irreversible aggregation, while the stability of the zwitterionic NPs was preserved only using a cryoprotectant. Therefore, we developed an alternative method for the NP concentration, based on the dialysis against a concentrated PEG solution. This method was optimized in terms of concentration factor (Fc), the ratio between the final and initial NP concentration, by acting on the PEG concentration in the dialysis medium, on its volume and on the initial NP concentration. With this approach, Fc up to 40 can be achieved in less than 10 h, preserving the possibility of redispersing the NPs to their original particle size distribution. Therefore, the dialysis proposed herein is a valuable alternative to lyophilization for the concentration of polymer NPs preserving their stability.
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