Unlock instant, AI-driven research and patent intelligence for your innovation.

Hybrid nano assembly for proteasome inhibition and sensitization photodynamic therapy as well as preparation and application of hybrid nano assembly

A nano-assembly and hybrid technology, which can be used in drug combinations, medical preparations with inactive ingredients, and medical preparations containing active ingredients, etc., can solve the problems of toxic and side effects, drug leakage, and low drug loading, and achieve Low toxicity and side effects, good stability and high drug loading

Active Publication Date: 2021-11-16
SHENYANG PHARMA UNIVERSITY
View PDF5 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] Based on the technical problems described in the background technology, the present invention further designs a photosensitizer in order to solve the problems of poor hydrophobicity of BTZ, poor solubility in water, low drug loading caused by entrapment in polymers, drug leakage and excipient-related toxicity. Nanoparticles formed by co-assembly with BTZ, so as to achieve technical effects such as high drug loading, good stability, and toxic and side effects, and then solve the poor therapeutic effect of a single pure drug and the quenching (ACQ) caused by the aggregation induction of photosensitizers effect, improving the combination therapy effect of chemotherapy and photodynamics

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Hybrid nano assembly for proteasome inhibition and sensitization photodynamic therapy as well as preparation and application of hybrid nano assembly
  • Hybrid nano assembly for proteasome inhibition and sensitization photodynamic therapy as well as preparation and application of hybrid nano assembly
  • Hybrid nano assembly for proteasome inhibition and sensitization photodynamic therapy as well as preparation and application of hybrid nano assembly

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0051] Example 1: Preparation of BTZ@PPa nanoparticles

[0052] Dissolve BTZ and pyropheophorbide a (PPa) in different molar ratios into 200 μL of tetrahydrofuran and ethanol volume ratio (1:1), and slowly add the solution dropwise to 2 mL of deionized water under stirring, PPa Uniform nanoparticles were formed spontaneously with BTZ, and then dialyzed in deionized water at 25°C to remove the organic solvent in the nano-preparation to obtain a nano-colloid solution without any organic solvent.

[0053] The particle size, particle size distribution and synergy index of BTZ and PPa of the prepared nano-preparation were detected, and the results are shown in Table 1.

[0054] Table 1. Particle size, particle size distribution and synergy index of BTZ and PPa of BTZ@PPa nanoparticles

[0055]

[0056] As shown in Table 1, the particle size of the nanoparticles is between 85-135nm, and the synergy index is 0.38-1.89. When BTZ:PPa=1:4, the distribution of BTZ@PPa nanoparticles ...

Embodiment 2

[0064] Example 2: Analysis of BTZ@PPa assembly mechanism

[0065] Through computer simulation, the mechanism of BTZ@PPa assembly was explored, and the molecular docking calculation was completed by using the Vina program of Yinfu cloud computing platform. The compound BTZ@PPa was energy minimized under the MMFF94 force field to obtain a 3D structure and form a stable nanoassembly. AutoDock Vina program was used for semi-flexible docking, the results are as follows image 3 As shown, there are various forces between PPa and BTZ molecules, such as π-π stacking, hydrophobic force, π-cation force, and hydrogen bonding force, which make great contributions to the assembly of PPa and BTZ.

Embodiment 3

[0066] Embodiment 3: the colloidal stability test of nanoparticle

[0067] The BTZ@PPa nanoparticles prepared in Example 1 and BTZ@PPa PEG 2K 1 mL of nanoparticles was taken out, added to 20 mL of phosphate buffered saline (PBS, pH 7.4) containing 10% FBS, incubated at 37°C for 12 hours, and at predetermined time points (0,1,2,4 , 6, 8 and 12 hours) by dynamic light scattering method to measure the particle size change. The result is as Figure 4 As shown, compared with non-PEG-modified BTZ@PPa nanoparticles, BTZ@PPa PEG 2K The nanoparticle colloid has good stability, and the particle size does not change significantly within 12 hours. PEG-modified BTZ@PPa nanoparticles are preferred.

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

PropertyMeasurementUnit
particle diameteraaaaaaaaaa
concentrationaaaaaaaaaa
Login to View More

Abstract

The invention discloses a carrier-free hybrid nano assembly as well as a preparation method and application thereof, and belongs to the field of new auxiliary materials and new dosage forms of pharmaceutical preparations. The carrier-free hybrid nano assembly is formed by co-assembling a porphyrin photosensitizer and bortezomib (BTZ), or is formed by co-assembling a porphyrin photosensitizer, BTZ and a PEG modifier. The carrier-free hybrid nano assembly provided by the invention has strong anti-tumor activity, and has very high safety. The co-assembled nano preparation disclosed by the invention provides a new strategy and more choices for developing the delivery of drugs and the combined application of photodynamic chemotherapy, and meets the urgent demand on efficient photochemical synergistic treatment in clinic.

Description

technical field [0001] The invention belongs to the technical field of new excipients and new dosage forms of pharmaceutical preparations, and specifically relates to the construction of co-assembled nanoparticles including porphyrin photosensitizer and proteasome inhibitor bortezomib (BTZ) and its application in drug delivery. Background technique [0002] Photodynamic therapy (PDT) has been extensively studied as a non-invasive cancer treatment with spatiotemporal selectivity and high safety. Photosensitizers (PSs) generate large amounts of reactive oxygen species (ROS) under tumor-localized laser irradiation. ROS cause oxidative damage to proteins, lipids, DNA, and other intracellular components, especially ROS-induced protein oxidative damage accelerates the functional inactivation and degradation of cellular biomacromolecules, eventually leading to tumor cell death. But there are multiple defense mechanisms in tumor cells, such as accelerated degradation of misfolded p...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
Patent Type & Authority Applications(China)
IPC IPC(8): A61K38/05A61K41/00A61K9/14A61K47/60A61P35/00
CPCA61K41/0071A61K38/05A61P35/00A61K41/0076A61K9/14A61K47/60A61K2300/00
Inventor 罗聪杨馥骏孙丙军李术萌何仲贵
Owner SHENYANG PHARMA UNIVERSITY