Drug delivery system modified with functionalized cell-penetrating peptide

A delivery system and functionalized technology, which is applied in the field of drug delivery system modified by functionalized penetrating peptides, can solve the problems of inability to enrich drugs, difficult drugs, and shortened drug circulation time, so as to improve the effect of anti-tumor therapy and increase the accumulation , the effect of good biosecurity

Pending Publication Date: 2020-02-11
FUDAN UNIV +1
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

The nano-drug delivery carriers such as: liposomes, lipid discs, nanoparticles, solid lipid nanoparticles, nanostructured lipid carriers, nanocomposites, micelles, etc., provide effective strategies for tumor treatment and have the potential to improve It has the advantages of bioavailability, prolonging the circulation time of drugs in the body, and reducing toxic and side effects, but the disadvantage is that the tissue penetration ability is poor, and the drug cannot be effectively enriched in the lesion.
[0003] The current research hotspot is the modification of functional targets on the surface of nano-drug delivery carriers, some of which are abou

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  • Drug delivery system modified with functionalized cell-penetrating peptide
  • Drug delivery system modified with functionalized cell-penetrating peptide
  • Drug delivery system modified with functionalized cell-penetrating peptide

Examples

Experimental program
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Example Embodiment

[0056] Example 1 Synthesis and identification of functionalized penetrating peptide-polyethylene glycol-phospholipid (CB5005-PEG-DSPE)

[0057] Dissolve an appropriate amount of CB5005 (CB5005-Cys) with cysteine ​​linked to the C-terminus in 0.1M PBS solution (pH 7.2), and take an appropriate amount of maleimide-polyethylene glycol-phospholipid (MaI-PEG-DSPE) ) Dissolved in dimethylformamide (DMF). The molar ratio of CB5005-Cys to Mal-PEG-DSPE is 1.2:1.0. After the two are mixed, they are reacted with magnetic stirring at room temperature for 2h. Excess CB5005-Cys and DMF have a molecular weight cutoff of The 3.5kDa dialysis bag was removed by dialysis and freeze-dried to obtain CB5005-PEG-DSPE. Using HPLC and 1 H-NMR characterization of the reaction product.

Example Embodiment

[0058] Example 2 Preparation of functionalized penetrating peptide modified nano drug delivery system

[0059] Preparation of liposomes containing fluorescent probe 5-carboxyfluorescein (FAM): the molar ratio of phospholipid (HSPC), cholesterol (Chol) and polyethylene glycol-phospholipid (mPEG2000-DSPE) is 52:43:5 Prepare liposomes (LS / FAM) containing 5-carboxyfluorescein (FAM), and simultaneously prepare CB5005- by mixing HSPC, Chol, mPEG2000-DSPE and CB5005-PEG-DSPE at a molar ratio of 52:43:3:2. LS / FAM. Weigh the above-mentioned membrane materials into eggplant-shaped flasks, add an appropriate amount of chloroform to completely dissolve the membrane materials, and remove the chloroform by rotary evaporation under reduced pressure to obtain a uniform lipid membrane. Then, the lipid membrane is placed in a vacuum drying oven to dry for 24 hours. Remove residual chloroform. Hydrate the lipid membrane with 5-FAM solution (dissolve 5-FAM powder in physiological saline and add an...

Example Embodiment

[0065] Example 3 Characterization of functionalized penetrating peptide modified nano drug delivery system

[0066] A laser scattering particle size analyzer was used to measure the particle size and distribution of the functionalized penetrating peptide modified nano-drug delivery system. The results showed that the particle size of the liposomes modified by CB5005 was about 500-800nm ​​before being extruded through the membrane. After extruding the membrane, the particle size of the liposomes modified by CB5005 was reduced to 100-150nm, the morphology was regular, and the polydispersity coefficient was less than 0.2, the surface is negatively charged or nearly neutral.

[0067] The lipid discs modified by CB5005 have a particle size of about 60nm, which is disc-shaped by cryo-electron microscopy, with a polydispersity coefficient of less than 0.3, and the surface is negatively charged.

[0068] Table 1. Characterization of Adriamycin Liposomes

[0069]

[0070] Table 2. Characteriz...

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Abstract

The invention belongs to the field of pharmaceutical preparations, and relates to a drug delivery system modified with a functionalized cell-penetrating peptide. According to the drug delivery system,the functional cell-penetrating peptide modifies the surface of nano drug delivery carriers such as a liposome, a lipid disc, a nanoparticle, a solid lipid nanoparticle, a nano-structured lipid carrier, a nanocomplex and a micelle. The cell-penetrating function of the cell-penetrating peptide can be adopted to help the nano drug delivery carriers penetrate through absorption barriers in a body and penetrate deep into tumor tissue to further deliver drugs into tumor cells. Meanwhile, the cell-penetrating peptide can further block an NF-[kappa]B pathway, has a cell nucleus localization function, can deliver carried chemotherapeutic drugs into the cell nucleus and exerts a synergistic antitumor effect. The targeted drug delivery system modified with the functionalized cell-penetrating peptide has good biological safety, can increase the accumulation of the drugs in tumor sites as a delivery carrier for the chemotherapeutic drugs and significantly improves the antitumor treatment effect of the chemotherapeutic drugs.

Description

technical field [0001] The invention belongs to the field of pharmaceutical preparations, and relates to a drug delivery system modified by a functionalized membrane-penetrating peptide; the drug delivery system is that the functionalized membrane-penetrating peptide is modified on a liposome, a lipid disc, a nanoparticle, or a solid lipid nanoparticle , nanostructured lipid carriers, nanocomposites, micelles and other nano-drug delivery carriers surface, using the membrane-penetrating function of membrane-penetrating peptides to help nano-drug delivery carriers penetrate the absorption barrier in the body and penetrate into the deep part of the tumor tissue. The drug is delivered to the inside of the tumor cell; at the same time, the functionalized penetrating peptide can also block the NF-κB pathway, and has the function of localizing the nucleus, and can deliver the chemotherapy drug carried by it to the nucleus to exert a synergistic anti-tumor effect; The targeted drug de...

Claims

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Application Information

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IPC IPC(8): A61K47/64A61K47/60A61K47/54A61K38/17A61K31/704A61K31/4745A61K31/17A61K9/127A61K45/00A61P35/00
CPCA61K47/64A61K47/60A61K47/54A61K38/17A61K31/704A61K31/4745A61K31/17A61K9/127A61K45/00A61P35/00A61K2300/00
Inventor 魏刚张燕宇张利林耀忠陆伟跃
Owner FUDAN UNIV
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