I prepare PLGA-Lipid hybrid nanoparticle by precipitation and solvent evaporation method. When I dilute these in deionized water the size remain same (observed by zetasizer or electron microscopy. But when I use PBS, saline or any buffer, I observe some coagulates, which precipitate. Please suggest me what can I add in the saline to prevent this precipitation.

I found this article, which states that lipid should be more cationic, so it can better hold the negative core of PLGA.

Article In Vitro Performance of Lipid-PLGA Hybrid Nanoparticles as a...

Although I have also read that charged nanoparticles are more prone to precipitate in presence of ions (Compared to sterically stabilized surface nanoparticles).

Please suggest me what can I add in the saline to prevent this precipitation. Thanks

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