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Chemotherapeutic drug-photosensitizer co-assembled nanoparticles and its construction

A technology of co-assembly and photosensitizer, applied in drug combination, pharmaceutical formulation, antineoplastic drugs, etc., can solve the problems of poor stability, low drug loading, toxic and side effects, etc.

Active Publication Date: 2021-07-16
SHENYANG PHARMA UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] With the development of nanotechnology, based on the existing formulation strategies, traditional nanocarriers can realize the co-encapsulation and delivery of chemotherapeutic drugs and photosensitizers, but there are problems such as low drug loading, poor stability, easy crystallization or leakage of drugs, and excipients. Toxic side effects and other issues

Method used

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  • Chemotherapeutic drug-photosensitizer co-assembled nanoparticles and its construction
  • Chemotherapeutic drug-photosensitizer co-assembled nanoparticles and its construction
  • Chemotherapeutic drug-photosensitizer co-assembled nanoparticles and its construction

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0034] Example 1: Preparation of non-PEGylated mitoxantrone-pyropheophytin a co-assembled nanoparticles

[0035] A certain amount of mitoxantrone (MTX) and pyropheophytin a (PPa) were dissolved in a mixed solvent (methanol / tetrahydrofuran=50 / 50, v / v) to prepare 10mM MTX stock solution and 10mM PPa stock solution .

[0036] When the molar ratio of chemotherapeutic drug to photosensitizer was 6:1, the mixed solution (900 μL MTX solution and 150 μL PPa solution) was added dropwise to 3 mL deionized water at a stirring speed of 900 rpm. The organic solvent was removed by rotary evaporation under the condition of 25° C., and a precipitate was precipitated.

[0037] When the molar ratio of chemotherapeutic drug to photosensitizer was 3:1, the mixed solution (450 μL MTX solution and 150 μL PPa solution) was added dropwise to 3 mL deionized water at a stirring speed of 900 rpm. The organic solvent was removed by rotary evaporation under the condition of 25° C. to obtain the co-assem...

Embodiment 2

[0044] Example 2: Preparation of PEG-modified Mitoxantrone-pyropheophytin a co-assembled nanoparticles

[0045] A certain amount of mitoxantrone (MTX), pyropheophytin a (PPa), PEG modifier DSPE-PEG 2000 (5wt%PPa)) was dissolved in a mixed solvent (methanol / tetrahydrofuran=50 / 50, v / v) to prepare 10mM MTX stock solution, 10mM PPa stock solution and 1.0mg / mL DSPE-PEG 2000 stock solution. When the molar ratio of chemotherapeutics and photosensitizer is 1:3, the mixed solution (50 μL MTX solution, 150 μL PPa solution and 33.3 μL DSPE-PEG 2000 solution) was added dropwise to 3 mL of deionized water. The organic solvent was removed by rotary evaporation under the condition of 25° C., and the PEG-modified mitoxantrone-pyropheophytin a co-assembled nanoparticles were obtained. The drug loadings of MTX and PPa were 43.3% and 53.6%, respectively, achieving efficient co-loading of chemotherapeutic drugs and photosensitizers. The particle size of PEG-modified mitoxantrone and pyropheop...

Embodiment 3

[0046] Example 3: FBS stability test of PEG-modified mitoxantrone-pyropheophytin a co-assembled nanoparticles

[0047] The PEG-modified mitoxantrone-pyropheophytin a co-assembled nanoparticles prepared in Example 2 were incubated at 37°C in PBS of pH 7.4 containing 10% FBS for 12h, and at predetermined time points (0, 2, 4, 6, 8, 10, 12h) The particle size change was measured by dynamic light scattering method. The result is as image 3 As shown, the PEG-modified mitoxantrone-pyropheophytin a co-assembled nanoparticles did not change significantly in particle size within 12 hours, showing good FBS stability.

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Abstract

The invention belongs to the field of new excipients and new dosage forms of pharmaceutical preparations. The chemotherapeutic drug-photosensitizer co-assembles nanoparticles and its construction. Rurubicin; the photosensitizer is a porphyrin-type photosensitizer selected from chlorin e6, hematoporphyrin monomethyl ether or chlorophyll derivatives. Wherein, the molar ratio of the chemotherapeutic drug to the photosensitizer is 3:1˜1:3. That is, a certain amount of chemotherapeutic drug and photosensitizer or a mixture of chemotherapeutic drug, photosensitizer and PEG is dissolved in an appropriate amount of organic solvent, and the solution is slowly added dropwise into water under stirring to spontaneously form uniform nanoparticles. The preparation process of the present invention is simple, easy to scale up production, and the particle size is small and uniform. Modification, can be modified by PEG to prolong the circulation time of nanoparticles in blood.

Description

technical field [0001] The invention belongs to the field of new excipients and new dosage forms of pharmaceutical preparations, and relates to the construction of chemotherapeutic drug-photosensitizer co-assembled nanoparticles and the construction thereof, in particular to the construction of a mitoxantrone-pyropheophytin a co-assembled nanoparticle and its application in drug delivery applications in the system. Background technique [0002] Cancer is a major disease that threatens human life and health. Chemotherapy is one of the effective strategies for cancer treatment, but most chemotherapeutic drugs have disadvantages such as low solubility, narrow therapeutic window, and certain toxic and side effects. With the continuous development of nanoscience in the field of medicine, in cancer treatment, nanomedicine such as Doxil (PEGylated doxorubicin liposome), Abraxane (paclitaxel albumin nanosuspension), Lipusu (paclitaxel liposome) And so on have been successfully lis...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K9/14A61K41/00A61K31/704A61K31/136A61P35/00
Inventor 孙进何仲贵王昭蒙孙孟驰
Owner SHENYANG PHARMA UNIVERSITY
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