Preparation method of targeting composite nanoparticle

Abstract

The invention discloses a preparation method of targeting composite nanoparticle. The invention uses phospholipids, pegylated phospholipids and polyethylene glycol-distearoyl phosphatidyl ethanolamine connected with RGD (arginine-glycine-aspartic acid) as an emulsifier, and uses a binary mixture solvent system of dichloromethane and ethanol to prepare the targeting composite nanoparticle which contains PLGA (poly lactic-co-glycolic acid) as the nucleus and contains the phospholipids and pegylated phospholipids as a shell by one-step emulsification method. The invention uses the hydroxyl camptothecin as a model drug to prepare the RGD targeting phospholipid-polymer composite nanoparticle with high drug loading rate (18.9%) and high entrapment efficiency (94.5%). The phospholipid monolayer and polyethylene glycol hydration layer located on the surface of the targeting composite nanoparticle prepared by the method provided by the invention can significantly reduce protein adsorption and extend the action time in vivo; the RGD connected with the shell of the composite nanoparticle can effectively promote nanoparticles specific binding to tumor cells or tumor new vessels with high expression of integrin, and improve the local drug concentration, so as to enable the targeting composite nanoparticles to have a better anti-tumor effect.

Description

technical field [0001] The invention belongs to the field of nano-medicine carriers, and in particular relates to a preparation process of targeted lipid-polymer composite nanoparticles and research on targeted nanoparticles loaded with hydroxycamptothecin. Background technique [0002] Malignant tumors are currently the most serious disease threatening human health and have become the number one cause of human death. At present, the treatment methods for malignant tumors mainly include surgery, chemotherapy, radiation therapy, etc. Among them, chemotherapy is the most suitable treatment method in addition to surgery in clinical practice, and its application is very common. Most chemotherapy drugs not only kill tumor cells, but also destroy normal tissues and cells, resulting in serious side effects. Therefore, the use of nanoparticles as drug carriers is one of the most effective means to reduce the toxic and side effects of chemotherapy drugs and improve the efficacy of d...

AI Technical Summary

Problems solved by technology

First of all, the solvent needs to be heated to 65 degrees Celsius during the preparation process, which is higher than the glass transition temperature of PLGA, which will affect the molecular chain of the carrier material. If it is used for the preparation of drug-loaded nanoparticles, it may affect the stability of the drug. properties and encapsulation efficiency; secondly, if drug-loaded nanoparticles are to be prepared by this method, it can only target drugs that can be dissolved in acetonitrile, which greatly limits the scope of its practical application, because the curative effect found so far is relatively good. Most of the anticancer drugs are strongly hydrophobic, such as: camptothecin, hydroxycamptothecin, doxorubicin, etc., these drugs are basically insoluble in acetonitrile and other polar solvents; Miscible solvents, the drug will also diffuse into the aqueous phase with the solvent, and the drug loading and encapsulation efficiency of the resulting product are low

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