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Temperature-sensitive phase-change fatty alcohol mediated amphiphilic drug delivery/controlled release carrier as well as preparation method and application thereof

A controlled-release carrier and fatty alcohol technology, applied in drug combinations, antineoplastic drugs, pharmaceutical formulations, etc., can solve problems such as drug leakage, normal tissue and cytotoxic side effects, achieve reduced damage, reduce the risk of drug leakage, and improve The effect of curative effect

Inactive Publication Date: 2018-08-03
HENAN UNIV OF SCI & TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the common problem with most drug carriers is that after intravenous injection into the body, during the delivery and blood circulation of chemotherapy drugs in the body, the drugs will inevitably leak out of the carrier, causing potential damage to normal tissues and cells. toxic side effects
[0007] At present, the use of temperature-sensitive phase-change fatty alcohols to prepare tumor drug delivery / controlled release carriers that can simultaneously achieve temperature stimulation-response "zero release state" and achieve co-delivery of chemotherapeutic drugs with different hydrophilic and hydrophobic properties has not been reported

Method used

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  • Temperature-sensitive phase-change fatty alcohol mediated amphiphilic drug delivery/controlled release carrier as well as preparation method and application thereof
  • Temperature-sensitive phase-change fatty alcohol mediated amphiphilic drug delivery/controlled release carrier as well as preparation method and application thereof
  • Temperature-sensitive phase-change fatty alcohol mediated amphiphilic drug delivery/controlled release carrier as well as preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0069] In this implementation, the temperature-sensitive hydrophilic drug delivery / controlled release carrier——hollow magnetic nano-ferric oxide / 1-pentadecanol / doxorubicin (HMNP / 1-15ALK / DOX) was prepared according to the following scheme Combined hyperthermia-chemotherapy for tumor-bearing nude mice under the action of variable magnetic field, the schematic diagram of the effect is as follows figure 1 shown.

[0070] 1. Preparation of folic acid grafted HMNP / 1-15ALK / DOX thermosensitive delivery / controlled release carrier:

[0071] (A) Dissolution of temperature-sensitive phase-change fatty alcohol 1-15ALK and encapsulation of hydrophilic chemotherapeutic drug DOX: put the beaker (100mL) in the oil bath of a heat-collecting magnetic stirrer, heat the temperature to 80°C, Then add the temperature-sensitive phase-change fatty alcohol (100mg) into the beaker, add chemotherapeutic drugs (1.2μg) after fully melting and fully magnetically stir (speed: 1000rpm, time: 5min) to complet...

Embodiment 2

[0083] In this implementation, the temperature-sensitive hydrophobic drug delivery / controlled release carrier-hollow Prussian blue nanocube / 1-hexadecanol / paclitaxel (HPB / 1-16ALK / PTX) was prepared according to the following scheme, and the opposite charge under the action of near-infrared laser Tumor-nude mice were treated with hyperthermia-chemotherapy, the schematic diagram of the effect is as follows: Figure 8 shown.

[0084] Preparation of membrane peptide RGD grafted HPB / 1-16ALK / PTX thermosensitive drug delivery / controlled release carrier:

[0085] (A) Dissolution of temperature-sensitive phase-change fatty alcohol 1-16ALK and encapsulation of hydrophobic chemotherapeutic drug PTX: put the beaker (200mL) in the oil bath of a heat-collecting magnetic stirrer, heat the temperature to 85°C, Then add the temperature-sensitive phase-change fatty alcohol (200mg) into the beaker, add chemotherapeutic drugs (2.4μg) after fully melting and fully magnetically stir (speed: 1000rpm,...

Embodiment 3

[0097] In this implementation, the temperature-sensitive amphiphilic drug delivery / controlled release carrier-hollow platinum-copper nanoframe / 1-iodonadecanol / doxorubicin & paclitaxel (HPCN / 1-I-19ALK / DOX&PTX) was prepared according to the following scheme Combined hyperthermia-chemotherapy for tumor-bearing nude mice under the action of near-infrared laser, the schematic diagram of the effect is as follows Figure 15 shown.

[0098] Preparation of Targeting Peptide TAT Grafted HPCN / 1-I-19ALK / DOX&PTX Amphipathic Thermosensitive Drug Delivery / Controlled Release Carrier:

[0099] (A) Dissolution of temperature-sensitive phase-change fatty alcohol 1-I-19ALK and co-encapsulation of hydrophilic chemotherapeutic drug DOX and hydrophobic chemotherapeutic drug PTX: put the beaker (200mL) in the oil bath of a heat-collecting magnetic stirrer In the pot, heat the temperature to 90°C, then add the temperature-sensitive phase-change fatty alcohol (200mg) into the beaker, add DOX2.4μg and ...

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Abstract

The invention relates to a temperature-sensitive phase-change fatty alcohol mediated amphiphilic drug delivery / controlled release carrier as well as a preparation method and an application thereof, and belongs to the field of nano biological materials. The carrier is prepared by encapsulating one or more hydrophilic / hydrophobic chemotherapy drugs in hollow nanoparticles on the basis of the amphiphilic property of temperature-sensitive phase-change fatty alcohol. The temperature-sensitive phase-change fatty alcohol mediated amphiphilic drug delivery / controlled release carrier provided by the invention is prepared by the following operations: dissolving the chemotherapy drugs in the temperature-sensitive phase-change fatty alcohol under a high-temperature oil bath condition; loading the dissolved chemotherapy drugs in cavities of the hollow nanoparticles under the action of a permeation assisting agent; collecting a drug carrier after centrifugal separation, washing and drying; and grafting tumor-targeted molecules onto the surface of the carrier, so that the tumor-targeted molecule grafted temperature-sensitive phase-change fatty alcohol mediated amphiphilic drug delivery / controlledrelease carrier is prepared. With the application of the drug carrier, co-delivery of various hydrophilic / hydrophobic chemotherapy drugs can be achieved; and the drug carrier, when applied to tumor resistance, can be combined with a thermotherapy action so as to kill and ablate tumor cells or solid tumors.

Description

technical field [0001] The invention belongs to the field of nano-biological materials, and in particular relates to a temperature-sensitive phase-change fatty alcohol-mediated amphiphile drug delivery / controlled release carrier, preparation and application thereof. Background technique [0002] The multifunctional nano-drug delivery / controlled release carrier with integrated diagnosis and treatment has become a new favorite in the research of precise tumor therapy, and has attracted more and more attention from researchers. However, the common problem with most drug carriers is that after intravenous injection into the body, during the delivery and blood circulation of chemotherapy drugs in the body, the drugs will inevitably leak out of the carrier, causing potential damage to normal tissues and cells. toxic side effects. In order to avoid the risk of leakage of chemotherapy drugs in vivo, a variety of different temperature "stimulus-response" substances are used for the ...

Claims

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Application Information

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IPC IPC(8): A61K47/10A61K31/704A61K31/337A61K41/00A61K47/18A61P35/00
CPCA61K31/337A61K31/704A61K41/0052A61K47/10A61K47/183A61P35/00A61K2300/00
Inventor 李景华张丰收宋卫东杨宪园鲍建峰周莹刘雪婷张悦
Owner HENAN UNIV OF SCI & TECH
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