The invention relates to the field of
drug delivery, and discloses a pH responsive lipid
nanoparticle for mRNA delivery, the lipid
nanoparticle comprises the following components: pH responsive lipid molecules with a
molar ratio of 30-50%; the invention also discloses a preparation method, which comprises the following steps: dissolving the pH-responsive lipid molecules,
cholesterol,
phosphatidyl ethanolamine and reduction-responsive lipid molecules in absolute ethyl
alcohol to prepare a lipid organic phase, and further comprises the following steps: dissolving the pH-responsive lipid molecules,
cholesterol,
phosphatidyl ethanolamine and reduction-responsive lipid molecules in absolute ethyl
alcohol to prepare the lipid organic phase. Through the
dual mechanism design of pH response and reduction response, the
delivery efficiency of mRNA is significantly improved,
phosphatidyl ethanolamine cooperates with pH response lipid to enhance
endosome escape ability and reduce responsive lipid to realize precise
cytoplasm release, and meanwhile, through lipid component optimization and preparation
process improvement, nanoparticles with controllable particle size and high stability are formed, and the preparation method is simple and easy to implement. The problems of low release efficiency and unstable structure in the prior art are effectively solved.