10-hydroxycamptothecine nanometer microsphere and preparation method thereof

Abstract

The invention discloses a 10-hydroxycamptothecin nano microsphere and a preparation method thereof. The preparation method of the 10-hydroxycamptothecin nano-microspheres is to dissolve the 10-hydroxycamptothecin nano-microspheres and PLGA in a binary solvent composed of ethanol or methanol and dichloromethane, and then mix them with the polyvinyl alcohol solution , emulsified, dispersed, centrifuged, and freeze-dried to obtain. Adopting the preparation method of degradable polymer-loaded 10-hydroxycamptothecin nano-microspheres of the present invention can greatly improve the application range of hydroxycamptothecin and polymer concentrations, use less organic solvents, and improve the drug-loading rate of the microspheres and high encapsulation efficiency, which can realize automation and large-scale production; the prepared 10-hydroxycamptothecin nanospheres can be released continuously for more than 10 days under the conditions of simulated phosphate buffer solution, greatly prolonging the 10-hydroxycamptothecin The action time of resin in the body is shortened, and the active lactone ring structure is well protected, almost 100% of which maintains the lactone ring structure.

Description

technical field [0001] The invention belongs to the field of biomedical materials, and in particular relates to a 10-hydroxycamptothecin nano-microsphere and a preparation method thereof. Background technique [0002] Camptothecin is a trace alkaloid extracted from the unique plant Camptotheca involucrata in my country. 10-Hydroxycamptothecin is the hydrogen of the 10th carbon atom of the camptothecin molecule replaced by a hydroxyl group, so it can be considered as a natural derivative of camptothecin. [0003] 10-Hydroxycamptothecin has a broad antitumor spectrum, and its anticancer effect is different from that of antimetabolites and alkylating agents. Studies have shown that 10-hydroxycamptothecin can selectively inhibit topoisomerase, thereby interfering with DNA replication, causing irreversible DNA strand damage, resulting in cell death. In addition, animal experiments have proved that 10-hydroxycamptothecin acts on the S phase and is a cell cycle-specific drug. Th...

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Problems solved by technology

[0004]10-Hydroxycamptothecin is easily soluble in dimethyl sulfoxide (DMSO), slightly soluble in methanol, chloroform, pyridine and other organic solvents, insoluble in water, its structure The α-hydroxylactone ring on the E ring is an essential active group, but this part will open the ring rapidly under alkaline conditions, which will reduce the curative effect and increase the toxicity

At present, most of the 10-hydroxycamptothecin used clinically in my country is an injection, which is reacted with sodium hydroxide to form a salt to dissolve it, and the lactone ring on the E ring in its structure is opened, so that the clinical application faces the following Many problems: (1) The injection form is HCPT sodium salt or ring-opening form, its metabolism is fast and the half-life is short; (2) HCPT sodium salt injection is unstable, and when the pH is greater than 7.4, it is easy to be hydrolyzed and inactivated, and it is easy to deactivate when exposed to light. Decomposition; (3) More than 95% of 10-hydroxycamptothecin fails to bind with serum protein in vivo, and the toxic side effects are stronger after binding

The preparation of nanoparticles by solvent evaporation requires a large amount of organic solvents, which is not conducive to environmental protection, and the particle size distribution is wide

Moreover, the encapsulation efficiency of the conventional solvent evaporation method is only 20-40% or lower, and the drug loading is also low, which limits the dosage

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