Conclusions
Results from this study potentially provide new insights into developing LPNs for mRNA based therapeutics.
Methods
We incorporated a series of biodegradable and biocompatible polymer materials into the formulation of TT3-LLNs to develop LPNs. mRNA delivery efficiency of different LPNs were evaluated and a systematic orthogonal optimization was further carried out.
Results
Our data indicate that PLGA4 (MW 24,000-38,000 g/mol) dramatically increased delivery efficiency of TT3-LLNs in comparison to other polymers. Further optimization identified PLGA4-7 LPNs (PLGA:mRNA=9:1, mass ratio; TT3:DOPE:Cholesterol:DMG-PEG2000=25:25:45:0.75, molar ratio) as a lead formulation, which displayed significantly enhanced delivery of two types of mRNA in three different human cell lines as compared with TT3-LLNs. Conclusions: Results from this study potentially provide new insights into developing LPNs for mRNA based therapeutics.