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Porphyrin lipid-perfluorocarbon nano preparation as well as preparation method and application thereof

A perfluorocarbon and porphyrin lipid technology, which is applied in the field of biomedical materials, can solve the problems of low perfluorocarbon loading capacity, light/acoustic drug aggregation, low generation capacity concentration, etc. Enhanced fluorescence/CT imaging and reduced toxicity and side effects

Active Publication Date: 2021-11-05
PEKING UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, their O 2 Intracellular H 2 o 2 low concentration limit
In contrast, perfluorocarbons (PFCs) have high biocompatibility and good oxygen solubility, and are expected to be used as artificial blood to deliver oxygen to relieve tumor hypoxia, but PFCs in conventional delivery systems load capacity is usually low, so an external stimulus is required to trigger oxygen release
On the other hand, most traditional photo / acoustic sensitizers have problems such as insufficient drug loading or serious self-aggregation of the embedded photo / acoustic drug, as well as early leakage of the drug during circulation, resulting in limited efficacy

Method used

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  • Porphyrin lipid-perfluorocarbon nano preparation as well as preparation method and application thereof
  • Porphyrin lipid-perfluorocarbon nano preparation as well as preparation method and application thereof
  • Porphyrin lipid-perfluorocarbon nano preparation as well as preparation method and application thereof

Examples

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Embodiment 1

[0038] The preparation method of a kind of porphyrin lipid-perfluorooctyl bromide nano-preparation of the present invention comprises the following steps:

[0039] 1) Porphyrin lipid A (where R 1 and R 2 Both are C16 alkyl; R 3 is hydroxyl; a=2, b=2; X is NH) (10mmol, PGL lipid) dissolved in a mixed solvent of chloroform and methanol (volume ratio 9:1), spin-dried under reduced pressure to form a thin film, vacuum dry overnight;

[0040] 2) Add ultrapure water, hydrate in a 60°C water bath for 30 minutes, and use an ultrasonic instrument to sonicate under ice bath conditions, so that the lipids are evenly dispersed in the aqueous solution;

[0041] 3) Add perfluorooctyl bromide (350 μL, PFOB) dropwise to the solution in step 2) under ice bath conditions, and use a probe to disperse ultrasonically for 5 minutes to obtain uniformly dispersed porphyrin lipid-perfluorooctyl bromide For the alkane nano-preparation, the centrifugation method (1000rpm) can be further used to remo...

Embodiment 2

[0044] The preparation method of a kind of porphyrin lipid-perfluorohexane nano-preparation of the present invention comprises the following steps:

[0045] 1) Porphyrin lipid B (where R 1 and R 2 Both are C12 alkyl; R 3 It is polyethylene glycol; a=2, b=2; X is O) (9.5mmol) and DSPE-mPEG2000 (0.5mmol) are dissolved in the mixed solvent of chloroform and methanol (volume ratio 9:1), minus Press and spin to dry the liquid to form a thin film, and vacuum dry overnight;

[0046] 2) Add ultrapure water, hydrate in a 45°C water bath for 10 minutes, and use an ultrasonic instrument to sonicate under ice bath conditions, so that the lipids are evenly dispersed in the aqueous solution;

[0047] 3) Add perfluorohexane (330 μL) dropwise to the solution in step 2) under ice bath conditions, and use a probe to disperse ultrasonically for 10 minutes at the same time to obtain a uniformly dispersed porphyrin lipid-perfluorohexane nano-preparation. The centrifugation method (1500rpm) can...

Embodiment 3

[0049] The preparation method of a kind of porphyrin lipid-perfluorohexane nano-preparation of the present invention comprises the following steps:

[0050] 1) Porphyrin lipid C (where R 1 and R 2 Both are C18 alkyl; R 3 For polyethylene glycol; a=3, b=3; X is O) (0.5mmol), DPPC (9.0mmol) and DSPE-Maleimide (0.5mmol) dissolved in chloroform and methanol (volume ratio 9:1) In the mixed solvent, the liquid was spin-dried under reduced pressure to form a thin film, and dried overnight in vacuum;

[0051] 2) Add ultrapure water, hydrate in a water bath at 50°C for 20 minutes, and use an ultrasonic instrument to sonicate in an ice bath, so that the lipids are evenly dispersed in the aqueous solution;

[0052] 3) Add perfluorohexane (352 μL) dropwise to the solution in step 2) under ice bath conditions, and use a probe to disperse ultrasonically for 10 minutes to obtain a uniformly dispersed porphyrin lipid-perfluorohexane nano-preparation. The centrifugation method (1500rpm) ca...

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Abstract

The invention discloses a porphyrin lipid-perfluorocarbon nano preparation and a preparation method and application thereof. The prepared nano preparation is of a core-shell structure, which comprises a porphyrin liposome membrane layer of a shell and perfluorocarbon of an inner core and can be used as a photosensitizer or sonosensitizer medicine and an oxygen delivery system, the photosensitizer / sonosensitizer medicine and oxygen are synchronously delivered to the tumor, under laser or ultrasonic irradiation, the photodynamic therapy / sonodynamic therapy effect is remarkably enhanced, the hypoxic microenvironment of the tumor is improved, and recurrence and metastasis of the tumor are effectively inhibited. According to the invention, photosensitizer / sonosensitizer medicine are covalently linked in lipid molecules, perfluorocarbon is entrapped through strong hydrophobic acting force, which has the characteristics of high stability, high drug loading capacity, high oxygen carrying capacity, difficulty in leakage and the like, and has a good clinical application prospect in tumor diagnosis and treatment.

Description

technical field [0001] The invention belongs to the field of biomedical materials, and in particular relates to a porphyrin lipid-perfluorocarbon nano-preparation and its preparation method and application. Background technique [0002] Photo / acoustodynamic therapy has attracted increasing attention in clinical cancer treatment research in the past decades. Usually photo / acoustodynamic therapy can transfer energy to O 2 , and then generate cytotoxic reactive oxygen species (ROS), thereby irreversibly destroying the protein or DNA of tumor cells and inducing tumor cell apoptosis. Compared with conventional surgery, chemotherapy, and radiotherapy, photo / acoustic dynamic therapy has the advantages of non-invasiveness, higher controllability, reduced side effects, negligible drug resistance, and precise therapeutic function preserving tumor intervention and replacing tumor ablation. [0003] However, so far, the clinical application of photo / acoustodynamic therapy is still aff...

Claims

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Application Information

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IPC IPC(8): A61K41/00A61K33/00A61K47/54A61K47/69A61K49/00A61K49/04A61P35/00A61P35/04
CPCA61K41/0033A61K41/0071A61K33/00A61K47/54A61K47/6929A61K49/0036A61K49/0052A61K49/04A61P35/00A61P35/04A61K2300/00
Inventor 戴志飞梁晓龙
Owner PEKING UNIV
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