Amphiphilic N-vinyl pyrrolidone-based polymers as PEG alternatives to avoid blood proteins adsorption around liposomes

Introduction: After a systemic administration, liposomes are quickly covered by proteins leading to the formation of a protein corona. This corona is responsible for a change of physicochemical properties (as an increase of the size), pharmacokinetics, biodistribution, targeting ability, … [1]. Polyethylene glycol (PEG) is generally grafted onto the liposomes surface to reduce these non-specific interactions with blood components [2]. Since PEG faces some issues [3], alternatives are searched which should optimally prevent the formation of this corona. The goal of this study is to evaluate the protein corona formation around cationic liposomes (DOTAP/Chol/DOPE 1/0.75/0.5 molar ratio) encapsulating a model siRNA.
Method: Different formulations were tested: naked liposomes, PEGylated liposomes (15% molar ratio of total lipids) and liposomes grafted with the new synthetic amphiphilic N-vinyl pyrrolidone-based polymers. Liposomes were incubated in FBS for two hours and their sizes were compared before and after incubation. Measurements were performed by DLS and NTA. An increase in liposomes size is related to the adsorption of proteins around the particles.
Results: Results show that 15% PEG allows to prevent a significant size increase. However, 15% amphiphilic N-vinyl pyrrolidone-based polymers are not able to prevent corona formation since both analyses revealed a huge increase of particles sizes. A higher concentration (40%) was necessary to hinder a significant size increase meaning probably that their insertion/coating into/onto lipoplexes is different compared to PEG.
Conclusions: To conclude, we showed that new synthetic amphiphilic N-vinyl pyrrolidone-based polymers were able to prevent protein corona formation around lipoplexes. Further studies are ongoing in order to evaluate the transfection capacity of these coated-vectors carrying siRNA.