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Placenta focus specific drug distribution and delivery system as well as preparation method and application thereof

A delivery system and specific technology, applied in the fields of chemistry and biomedical engineering, can solve problems such as deficiency, and achieve the effect of reducing tissue distribution and release, structural stability, and reducing toxic and side effects

Active Publication Date: 2022-04-19
THE FIRST AFFILIATED HOSPITAL OF SUN YAT SEN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0008]In summary, there is currently a lack of nanocarriers that can effectively avoid non-specific drug absorption by mothers and fetuses, and then achieve specific drug delivery and functional regulation of TB cells in the placenta system

Method used

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  • Placenta focus specific drug distribution and delivery system as well as preparation method and application thereof
  • Placenta focus specific drug distribution and delivery system as well as preparation method and application thereof
  • Placenta focus specific drug distribution and delivery system as well as preparation method and application thereof

Examples

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preparation example Construction

[0040] The present invention also provides a preparation method of the above-mentioned placental focus-specific drug distribution delivery system, comprising the following steps:

[0041] S1. Load superparamagnetic iron ferric oxide SPIO nanoparticles, small molecule drugs and / or genes that regulate the function of placental trophoblast cells to the copolymer to obtain composite nanoparticles;

[0042] S2. Linking placental trophoblast cell surface marker antibodies to composite nanoparticles;

[0043] S3, linking the enzyme substrate polypeptide that promotes placental development and fetal nutrition to PEG to obtain polypeptide-PEG;

[0044] S4, mixing the polypeptide-PEG and liposomes to form a lipid bimolecular membrane modified by polypeptide-PEG;

[0045] S5. Assembling the polypeptide-PEG modified lipid bimolecular membrane and composite nanoparticles into a placental lesion-specific drug distribution delivery system.

[0046] Preferably, in step S1, the mass ratio of...

Embodiment 1

[0056] S1. Synthesis of polyacetylimide-grafted polyethylene glycol (PEG-PEI).

[0057] Polyethyleneimine-grafted polyethylene glycol (PEG-PEI) was synthesized by a two-step method. First, the terminal hydroxyl groups of monomethyl ether polyglycol were activated with carbonyldiimidazole, and then reacted with the amino groups of polyethyleneimine to generate PEG. -PEI.

[0058] The specific operation is as follows: weigh monomethyl ether glycol (8.0 g, Mn=2 kDa) into a reaction flask, dry it in vacuum at 80° C. for 6 h, and add THF (60 mL) under an argon atmosphere to dissolve it. Weigh carbonyldiimidazole (CDI, 6.4g) and another reaction bottle, then slowly drop THF dissolved in mPEG-OH into the CDI bottle with a constant pressure dropping funnel, and stir the reaction overnight at room temperature. Distilled water (0.648 mL) was added to inactivate excess CDI, and stirring was continued for 30 min. Precipitate the solution into a large amount of cold ether, filter and dry...

Embodiment 2-4， comparative example 1-6

[0079] Compared with Example 1, Example 2-4 or Comparative Example 1-6 can be prepared by changing the dosage of polymer, drug and SPIO in Step S3 or omitting a certain step in Steps S3, S4, S5, S6, and S7 , see Table 1 below for details.

[0080] Table 1: Examples and comparative examples.

[0081]

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Abstract

The invention relates to a placenta focus specific drug distribution delivery system and a preparation method and application thereof, and belongs to the technical field of chemical and biomedical engineering.The delivery system is of a core-shell double-layer structure and comprises an outer shell and an inner core; the shell is an enzyme substrate polypeptide-PEG modified lipid bimolecular membrane which is subjected to targeted disintegration under the action of an enzyme which is in contact with placenta tissue interstitial fluid and is highly expressed; the inner core is a drug carrier modified by a marker antibody with high specific expression on the surface of the placenta trophoblast, and superparamagnetic ferroferric oxide SPIO nanoparticles and a small molecule drug or / and a therapeutic gene for regulating and controlling the function of the placenta trophoblast are loaded in the drug carrier. The nano-drug delivery system disclosed by the invention can effectively avoid non-specific drug absorption of other organs outside the placenta of the maternal body and a fetus, so that delivery and function regulation and control of specific drugs of trophoblasts in the placenta are realized.

Description

technical field [0001] The invention belongs to the technical fields of chemistry and biomedical engineering, and in particular relates to a placental lesion-specific drug distribution and delivery system, its preparation method and application. Background technique [0002] Preeclampsia (PE, hypertension during pregnancy) is a common major perinatal disease, which refers to the occurrence of elevated blood pressure and proteinuria after 20 weeks of pregnancy, and severe cases develop into convulsions or coma, seriously endangering pregnant women and children. Fetal safety is the second leading cause of maternal death. Studies have found that during the development of PE, the angiogenesis and other functions of the placenta are severely deficient, which is rooted in the impairment of the EMT and angiogenesis-promoting functions of placental trophoblast cells (trophoblast cells (TB) [Int JMol Sci.2021Sep 7; 22(18 ):9675. doi:10.3390 / ijms22189675.]. However, there are no eff...

Claims

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Application Information

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IPC IPC(8): A61K47/69A61K47/68A61K47/64A61K31/715A61K31/09A61K41/00A61P9/12A61P15/00B82Y5/00
CPCA61K47/6911A61K47/64A61K47/6849A61K47/6937A61K31/715A61K31/09A61K41/00A61P9/12A61P15/00B82Y5/00
Inventor 王晶王子莲郭宇王伟伟王霁朏杨佳丽
Owner THE FIRST AFFILIATED HOSPITAL OF SUN YAT SEN UNIV
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