Ternary composite nano system based on methoxy polyethylene glycol-polylactic acid and application of ternary composite nano system

Abstract

The invention relates to a ternary composite nano system based on methoxy polyethylene glycol-polylactic acid / polyethylene glycol vitamin E succinate and a derivative thereof / poloxamer . The ternary composite nano system has a diversified structure and is used for carrying out single loading or multidrug co-loading on various types of hydrophobic and hydrophilic drugs, the particle size is 50 to 100 nm, and the drug loading capacity and the encapsulation efficiency are high. The ternary composite nano system can be swallowed into cells through passive targeting of EPR (Enhanced Permeability and Retention Effect), excretion of MDR (Multidrug Resistance) protein on drugs can be avoided, and meanwhile, the polyethylene glycol vitamin E succinate and the derivative thereof have different-mechanism anti-MDR function with the poloxamer, so that the ternary composite nano system is capable of realizing mutual supplementation of multiple different anti-MDR mechanisms, and has a better anti-MDReffect.

Description

technical field [0001] The invention belongs to the field of pharmaceutical preparations, and relates to a ternary composite nano system based on methoxypolyethylene glycol-polylactic acid and its application. Background technique [0002] Multidrug resistance (MDR) refers to the long-term exposure of tumor cells to a certain chemotherapeutic drug, which not only produces resistance to this chemotherapeutic drug, but also produces cross-resistance to other chemotherapeutic drugs with different structures and functions. . At present, the occurrence of multidrug resistance is not limited to tumor chemotherapy drugs, anti-infective drugs and a variety of oral drugs also have MDR phenomenon, which greatly reduces the efficacy of drugs. The causes of MDR are extremely complex, and the overexpression of the ABC (Adenosinetriphosphate-binding cassette, ABC) membrane transport pump is the most important reason for the generation of MDR. The ABC family related to MDR has 48 members....

AI Technical Summary

Problems solved by technology

However, the binary composite nanosystem based on MPP has the following limitations: (1) the particle size is too large

In the MPP binary system, because the interaction between MPP and another polymer is often weak, the nanosystem is relatively loose, and the drug in the carrier is easy to release during the preparation process and blood circulation, which is not conducive to its reaching the lesion. play a therapeutic role

(3) Drug loading and encapsulation efficiency are not high

In the MPP binary system, the weak force between MPP and another polymer makes the nanosystem relatively loose. At the same time, the weak force between MPP and another polymer and the drug makes the MPP binary The system cannot effectively entrap the drug

(4) Weak anti-multidrug resistance

Due to the complexity of the mechanism of multidrug resistance, the anti-multidrug resistance mechanism of only one polymer is often unable to effectively suppress the problem of multidrug resistance, and the effect of improving drug treatment effect is limited

(5) The stability is not high

Although hydrophilic drugs do not have the problem of poor solubility, problems such as systemic toxicity, immediate release, and poor targeting still exist

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