SN-38-PLGA sustained release microsphere for intratumoral injection and preparation method and application thereof

Abstract

The invention provides an SN-38-PLGA sustained release microsphere for intratumoral injection and a preparation method and application thereof. SN-38 is used as a model drug, PLGA is used as a carriermaterial, the SN-38-PLGA sustained release microsphere capable of being available for intratumoral injection dose is successfully built by adopting an emulsification-solvent evaporation method, and the SN-38-PLGA sustained release microsphere has the advantages of smooth and rounded surface, moderate particle size and high encapsulation efficiency and drug-loading capacity and the like; and meanwhile, the SN-38-PLGA sustained release microsphere for the intratumoral injection can enable the SN-38 to maintain effective high concentration for a long time in a tumor area, inactivation of the SN-38 drug is effectively avoided, and thus good practical application value is achieved.

Description

technical field [0001] The invention belongs to the technical field of pharmaceutical preparations, and in particular relates to SN-38-PLGA sustained-release microspheres for intratumoral injection and a preparation method and application thereof. Background technique [0002] The information disclosed in this background section is only intended to increase the understanding of the general background of the present invention, and is not necessarily taken as an acknowledgment or any form of suggestion that the information constitutes the prior art already known to those skilled in the art. [0003] At present, the morbidity and mortality of cancer are increasing year by year, posing serious threats and challenges to human health and life. Its pathogenesis is extremely complicated, and factors such as genetics, environment, even eating habits and psychological burden all play a very important role in it. In recent years, with the development of pharmacology, pharmacy, molecul...

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Problems solved by technology

[0004] As a broad-spectrum anticancer drug, irinotecan has a strong inhibitory effect on a variety of cancer cells, but it must be converted into 7-ethyl-10-hydroxycamptothecin (SN -38) to show anti-tumor effect, unfortunately, the conversion efficiency is only 2% to 8%, can not be efficiently utilized to a certain extent, resulting in great waste

[0005] Moreover, although the activity of SN-38 is very high (studies have pointed out that the therapeutic effect of SN-38 is about 1000 times that of its prodrug irinotecan), some chemical and pharmacological characteristics of itself limit its clinical application. Application: First, SN-38 has poor solubility and is almost insoluble in water (11-38μg / ml), so it has poor druggability, and no successful SN-38 preparation has been developed so far; secondly, the E ring of SN-38 The ester ring structure has reversible pH-dependent hydrolysis, and the E ring can maintain a stable lactone ring structure under acidic conditions, while the E ring will rapidly open to form a carboxylate structure under alkaline conditions, resulting in SN-38 Loss of anti-tumor activity, while human physiological conditions are alkaline, this feature also limits the application of SN-38 in anti-tumor

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