Preparation method of drug-loaded nano-micelles with long-time ocular surface retention and high cornea permeability

Abstract

The invention discloses a preparation method of drug-loaded nano-micelles with long-time ocular surface retention and high cornea permeability. The preparation method utilizes the property that the ocular surface has a negatively-charged adhesive protein layer, and by grafting polypeptide on the surface of the nano-micelles, the nano-micelles present the property of positive charge in a tear environment through the design of the polypeptide since the polypeptide has the property of amphoteric dissociation, so that the interaction between the nano-particles and ocular surface tissues is increased, the ocular surface retention and corneal permeability of the drug are increased, and the drug carrier can be used for the treatment of ocular and intraocular diseases after being loaded with different hydrophobic drugs.

Description

technical field [0001] The invention specifically relates to the technical field of ophthalmic drugs, in particular to a preparation method of drug-loaded nano micelles with long ocular surface retention and high corneal penetration. Background technique [0002] Low bioavailability is a key problem common in clinical ocular surface drugs. The eyeball is a relatively independent tissue with obvious differences in structure and microenvironmental characteristics from other parts, as well as special drug delivery and metabolism pathways, thus bringing unique challenges to ocular medications that are different from other parts: 1) There is a blood-ocular barrier, which is difficult to Use systemic administration to achieve therapeutic concentrations; 2) The immune immunity of the eyeball, traumatic local administration is prone to intraocular infection; 3) There are ocular surface structural barriers (relatively closed multi-layer film structure) and physiological barriers (suc...

AI Technical Summary

Problems solved by technology

Studies have shown that only 1-3% of the drug can reach the intraocular tissue in the traditional eye drop administration method, and most of the drug is discharged through the nasolacrimal duct, which not only causes a waste of drugs, but also has the risk of secondary damage

We believe that there are at least three distinct and interrelated factors that limit the efficacy of the drug: 1) The structural characteristics of the eyeball's multi-layered membrane closure limit the drug's entry into the eye; 2) Normal physiological activities such as tear circulation and blinking make the drug rapidly Excretion, reducing the contact time of the drug with the ocular surface, thereby affecting the corneal permeability of the drug; 3) The short residence time of the hydrophobic drug on the ocular surface and the low tear solubility further lead to low bioavailability of the drug

Hydrophobic drugs such as FK506 (tacrolimus, often translated as tacrolimus), dexamethasone, cyclosporine, etc. are commonly used eye drugs, and their bioavailability is low when used directly

Hydrophobic drug-loaded tears have low solubility and usually exist in the form of a suspension (small particles), resulting in a decrease in the specific surface area for the drug molecule to contact and interact with the ocular surface, thereby affecting ocular surface residence time and corneal penetration properties

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