Double-drug-loading carrier-free nanoparticle and preparation method thereof

A carrier-free, dual-drug-loading technology, applied in the field of medicine, can solve problems such as the inability to get rid of the dependence on synthetic carrier materials, the inability to efficiently load drugs, and safety issues, and achieve synergistic anti-tumor, good biocompatibility and biological Safety, the effect of avoiding toxic and side effects

Pending Publication Date: 2020-01-10
LIAOCHENG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] Most of the existing nano drug delivery systems still cannot get rid of the dependence on traditional synthetic carrier materials

Method used

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  • Double-drug-loading carrier-free nanoparticle and preparation method thereof
  • Double-drug-loading carrier-free nanoparticle and preparation method thereof
  • Double-drug-loading carrier-free nanoparticle and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0030] Example 1 Preparation of 7-ethyl-10-hydroxycamptothecin (SN38) / chlorin e6 (Ce6) dual drug-loaded carrier-free nanoparticles (SN38 / Ce6 NPs): accurately weigh 7.6 mg of SN38 powder and 3.8 mg Ce6, dissolve in 1 mL DMF, ultrasonically dissolve to form an organic phase; the above organic phase is added dropwise to 15 mL of deionized water under 250 W ultrasonic conditions, the temperature is controlled below 20 °C, and the ultrasonic is continued for 10 minutes , Dialysis to remove the organic solvent (ie, the mixed liquid after the organic phase and the water phase are mixed); high pressure homogenization under 150 MPa pressure 3 times, 1.5 min each time, SN38 / Ce6 NPs are obtained. Dynamic light scattering (DLS) measures its particle size. Add 1% (w / v%) of the lyophilized protective agent lactose to the SN38 / Ce6 NPs solution and freeze-dry for 12 h to obtain SN38 / Ce6NPs lyophilized powder. SN38 / Ce6 NPs freeze-dried powder is reconstituted with water or 5% glucose. DLS mea...

Embodiment 2

[0032] Example 2 Scanning electron microscopy (SEM) was used to observe the morphology of dual drug-loaded carrier-free nanoparticles: SN38 / Ce6 NPs prepared according to Example 1 were freeze-dried without lyophilization protection agent, and the lyophilized powder was electrically conductive The glue is fixed on the copper column and sprayed with gold for 240 s under vacuum and 30 mA current. Observe under scanning electron microscope.

[0033] The SN38 / Ce6 NPs observed in Example 2 showed a regular rod-like structure ( figure 2 ), the length and diameter of the nanorods are relatively consistent, with an average length of 250 nm and a diameter of about 20 nm. Since the particles in the solution are assumed to be spherical during DLS measurement, the measured particle size is the equivalent volume particle size. Therefore, the results of SEM and DLS will slightly deviate.

Embodiment 3

[0034] Example 3 The dynamic membrane dialysis method was used to determine the in vitro release curve of dual drug-loaded carrier-free nanoparticles: Three batches of SN38 / Ce6 NPs were prepared according to Example 1, and SN38 injection and Ce6 injection (self-made with alkalized water) were used as controls. Dilute with deionized water to a SN38 concentration of 25 µg / mL and a Ce6 concentration of 12.5 µg / mL to conduct an in vitro release test. Precisely draw 2 mL of medicated solution, put it into a dialysis bag (MWCO=8000~14000) soaked in distilled water, tie the bag tightly, add 100mL 0.01 M PBS (including 1% SDS), and place it in a 37 °C water bath Release in a constant temperature oscillator (100 rpm). At preset time points (0.0833, 0.25, 0.5, 1, 2, 4, 6, 8, 10, 12, and 24 h), 5 mL was sampled, and an isothermal and equal volume of release medium was added at the same time. Calculate the cumulative drug release percentage based on the measured drug concentration and dra...

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Abstract

The invention discloses a double-drug-loading carrier-free nanoparticle preparation and a preparation method thereof. The double-drug-loading carrier-free nanoparticle is not added with any carrier and is only composed of a phototherapy drug and a chemotherapy drug, and the phototherapy drug is a drug with photosensitizer properties, namely chlorin e6; wherein the chemotherapeutic drug is a camptothecin drug, and the camptothecin drug is one of camptothecin, 10-hydroxycamptothecine or 7-ethyl-10-hydroxycamptothecine. The double-drug-loading carrier-free nanoparticles are prepared by combiningan anti-solvent precipitation method with a high-pressure homogenization method or combining an alkali dissolution and acid precipitation method with the high-pressure homogenization method, the particle size is 140-170 nm, a freeze-drying protective agent can be added for freeze-drying, and the particle sizes before and after freeze-drying redissolution have no significant difference. According to the double-drug-loading carrier-free nanoparticles, the synergistic effect of phototherapy-chemotherapy is achieved, the anti-tumor effect is remarkable, meanwhile, the problems of safety, unclear in-vivo metabolism and the like caused by carrier synthesis are avoided, the biocompatibility is good, and the potential clinical application value is achieved.

Description

Technical field [0001] The invention belongs to the technical field of medicine, and specifically relates to a dual-drug carrier-free nanoparticle preparation, in particular to a dual-drug carrier-free nanoparticle that integrates photodynamic therapy and chemotherapy and a preparation method thereof. Background technique [0002] Malignant tumor is a major disease threatening human health and life. It can destroy the structure and function of human tissues and organs, causing necrosis, bleeding and infection, and patients may eventually die due to organ failure. The current treatments for tumors are mainly surgery, radiotherapy and chemotherapy. Surgical treatment is mainly for solid tumors and other tumors that have not yet spread, and there are certain sequelae and dysfunction after surgery. The cycles of radiotherapy and chemotherapy are relatively long and have certain limits. They are prone to have relatively large toxic and side effects during treatment, which can cause g...

Claims

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Application Information

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IPC IPC(8): A61K41/00A61K31/4745A61K47/69A61K47/55A61P35/00
CPCA61K31/4745A61K41/0071A61K47/55A61K47/6929A61P35/00A61K2300/00
Inventor 赵燕娜赵玉萍刘敏丁壮韩军
Owner LIAOCHENG UNIV
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