The invention discloses a preparation method of a non-
Newtonian fluid-based temperature-shear
dual response type ophthalmic sustained-release
drug carrier, and belongs to the technical field of ophthalmic medicines. The preparation is composed of a dispersed phase (a
temperature response type targeting nano-
drug carrier) and a continuous phase (a non-
Newtonian fluid matrix), wherein the
mass fraction of the dispersed phase in the continuous phase is 0.5-2%. The
temperature response type targeted nano-
drug carrier is of a core-shell two-layer structure, the core is composed of a
PLGA-PEG
copolymer and an active drug, the shell is formed by
grafting poly N-isopropylacrylamide (PNIPAM) and
hyaluronic acid, and the lowest critical solution temperature (LCST) of the PNIPAM is 35-37 DEG C; the non-
Newtonian fluid matrix is a pseudoplastic fluid, is composed of Carbomer 940 and
triethanolamine, and has a
shear thinning characteristic. The preparation method comprises the following three steps: preparation of the
temperature response type targeting nano-
drug carrier, preparation of the non-Newtonian fluid matrix and low-speed dispersion and compounding of the two. According to the invention, shear-response convenient administration, temperature-response precise
drug release and long-acting retention synergism are realized, the
bioavailability of the drug and the compliance of a patient are remarkably improved, the stability is excellent, the preparation process is simple and controllable, and the preparation method is suitable for long-acting
targeted therapy of chronic eye diseases such as
allergic conjunctivitis, chronic
xerophthalmia,
glaucoma and the like.