The invention discloses composite lipid nanoparticles as well as a preparation method and application thereof. The composite lipid
nanoparticle comprises a lipid outer layer and an internal
drug loading core, the lipid outer layer comprises
lecithin,
cholesterol, DSPE-PEG2000 and DSPE-PEG2000-CREKA, and the internal
drug loading core comprises
fatty acid and a
protein thrombolytic drug. The preparation method comprises the following steps: forming a lipid membrane, preparing a water-phase solution, hydrating the lipid membrane, extruding, filtering and the like.
Thrombus targeting is achieved through a CREKA
peptide mediated
protein crown formation mechanism, the
drug encapsulation efficiency is improved to 26.55% through
fatty acid, and drug leakage is reduced. The composite lipid nanoparticles provided by the invention have good
biocompatibility, can effectively dissolve
thrombus and remarkably reduce the bleeding risk, and can be used for preparing medicines for treating
thrombus obstructive diseases.