CN102688223A - Anti-cancer drug-loading nanofiber film and preparation method thereof - Google Patents
Anti-cancer drug-loading nanofiber film and preparation method thereof Download PDFInfo
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- CN102688223A CN102688223A CN2012101911421A CN201210191142A CN102688223A CN 102688223 A CN102688223 A CN 102688223A CN 2012101911421 A CN2012101911421 A CN 2012101911421A CN 201210191142 A CN201210191142 A CN 201210191142A CN 102688223 A CN102688223 A CN 102688223A
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Abstract
The invention relates to an anti-cancer drug-loading nanofiber film and a preparation method thereof. The nanofiber film is composed of a loading drug and a substrate, wherein a photosensitizer and a chemotherapeutic drug in a molar ratio of 1:(1-2) are used as the loading drug of the nanofiber film; a biodegradable high molecular material is used as the substrate of the nanofiber film; and the total drug mass is 4% of the substrate mass. The preparation method comprises the steps of: (1) adding the chemotherapeutic drug to glacial acetic acid, heating to dissolve the drug to obtain a chemotherapeutic drug solution; adding the photosensitizer and the biodegradable high molecular material into an organic solvent, uniformly stirring, and then adding the chemotherapeutic drug solution to prepare a high polymer solution; and (2) carrying out electrostatic spinning on the high polymer solution, and volatilizing the organic solvent and the glacial acetic acid to obtain the anti-cancer drug-loading nanofiber film. The anti-cancer drug-loading nanofiber film can be used as a wound dressing at an operation wound for preventing infection, stopping bleeding and promoting healing of the operation wound; and the preparation method has the advantages of simplicity in operation, low cost, good drug slow-release performance and broad application prospect.
Description
Technical field
The invention belongs to composite nano fiber and preparation field thereof, particularly a kind of loaded with anti-cancer medicine nano fibrous membrane and preparation method thereof.
Background technology
Tumor is serious threat human life's commonly encountered diseases, a frequently-occurring disease.According to the WHO statistics, in 6,000,000,000 populations of the whole world, die from malignant tumor person every year on average and reach 6,900,000 people, new cases 8,700,000, and numeral is also increasing year by year.China's tumor patient reaches 1,800,000 people at present, and mortality rate accounts for second in all causes of disease.Therefore, countries in the world government, research institution and drugmaker pay close attention to the research of anti-tumor medicine and Therapeutic Method always and support.At present, treat tumor method commonly used clinically chemotherapy, X-ray therapy and excision therapy etc. are arranged.Chemotherapy is because side effect is big, and patient is difficult to the withstand prolonged treatment, makes curative effect restricted; X-ray therapy then exists the part tumor still can not be by the problem of part control after improving radiological dose; Main cause is to exist in many tumors the insensitive anoxic cell of ray; For enhancing treatment effect often need increase radiological dose,, radiological dose will damage normal structure but surpassing certain limit.
The excision therapy is the most frequently used method, but often has residual tumor cell after the operation, thereby causes the recurrence of cancer, has seriously restricted the actual efficacy of this therapy.The main method that at present is used for addressing this problem clinically has repeat surgery and chemotherapy.These two kinds of methods exist following problem:
1, the repeat surgery expense is high, and is big to patient's injury.Because the cancer patient is in all tired states of body and mind behind the process operative treatment, the treatment that undergos surgery once more in a short time bring great wound and misery can for patient's body and mind, and the repeat surgery expense is high, all is heavy financial burden to patient family and country.
2, the clinician applies antitumor drug at tumor locus and is used for eliminating the tumors remaining cell after operation, and this method is extremely extensive, accurately dose.Most of antitumor drug all have big lethal effect to normal cell, so the selection of dose is of crucial importance, otherwise that drug level can cause that too greatly then patient poisons is then invalid very little; In addition, adopt this method medicine can't slow release at tumor locus, the violent release of medicine or can cause patient's poisoning perhaps can make the effective time of medicine very short, and drug level is well below its valid density when tumor recurrence.And exist in the tumor tissues the insensitive anoxic cell of chemicotherapy, this just need keep certain drug level so that can eliminate the tumor cell of recurrence at any time through slow release method is long-term at operative site.
Therefore; Study that a kind of side effect is little, selectivity is high, eutherapeutic invasive methods carries out the targeting spike and treatment, eliminate residual tumor cell; Reducing the recurrence and the transfer of tumor, is the important and urgent advanced subject that current international medicine and pharmacology interface is faced.
Method of electrostatic spinning is a polymeric spray static stretch spinning method, with on polymer solution or the melt band several thousand to volt high-pressure electrostatics up to ten thousand, charged polymer liquid drops under the effect of electric field force and is accelerated at Taylor conical point capillaceous.When electric field force was enough big, the polymer drop overcame surface tension and forms the injection thread; Thread is solvent evaporation or curing in course of injection, finally drops on the receiving system, forms the fiber felt of similar non-weaving cloth shape.The fiber that the electricity consumption spining technology makes, its diameter can reach nanoscale, and specific surface area is big, fiber thickness degree and homogeneity height, draw ratio are big.
United States Patent (USP) (US20020181640) in 2002, Ignatious and Baldoni two people's electricity consumption spinning nanofibers design have respectively fast, instant, time-delay, slowly, continue and the composite drug of different drug release features such as stage.2004; Daniel J.Smith and Darrell H.Reneker two people have announced a patent (US20040595329); Their electricity consumption spinning has made the nanofiber that straight chain gathers (Ethylenimine) nitrous azanol, as a kind of external coating film of novel medical device.This overlay film can slowly and balancedly discharge nitric oxide (NO), promotes the rehabilitation of organizing of medical device periphery, and prevents that hard thing from causing further injury to organizing periphery.This method has opened up a new application for the electrospinning fibre medicine carrying.
Summary of the invention
Technical problem to be solved by this invention provides a kind of loaded with anti-cancer medicine nano fibrous membrane and preparation method thereof, and the wound dressing that this nano fibrous membrane can be used as the surgical wound place is used for protecting from infection, stopping blooding, and promotes the healing of surgical wound; After operation, at first through the anticancer chemotherapeutic agent kill cancer cell; Then, further, make photosensitizer generation drug effect, thereby non-toxic efficient, remove the tumors remaining cell easily, prevent the recurrence of tumor, reach the purpose of radical cure cancer through fiber orientation irradiation.
A kind of loaded with anti-cancer medicine nano fibrous membrane of the present invention; Said nano fibrous membrane is made up of medicine carrying and matrix; Wherein, The photosensitizer and the chemotherapeutics that with the mol ratio are 1:1 ~ 2 are as the nano fibrous membrane medicine carrying, and with the matrix of Biodegradable polymer material as nano fibrous membrane, the medicine gross mass is 4% of a substrate quality.
Said photosensitizer is Verteporfin or tetramethyl porphin.
Said chemotherapeutics is 5-fluorouracil or methotrexate.
Said Biodegradable polymer material is polylactic acid (PLLA), PETG (PET), polyglycolic acid (PGA) or polycaprolactone (PCL), and molecular weight is 8W-30W.
The method for preparing of a kind of loaded with anti-cancer medicine nano fibrous membrane of the present invention comprises:
(1) chemotherapeutics is joined in the glacial acetic acid, heating makes medicine dissolution, obtains chemotherapeutics solution; Photosensitizer and Biodegradable polymer material are joined in the organic solvent, stir, add chemotherapeutics solution then, be mixed with high polymeric solution;
(2) above-mentioned high polymeric solution is carried out electrostatic spinning, volatilization organic solvent and glacial acetic acid make the loaded with anti-cancer medicine nano fibrous membrane.
The mass ratio of chemotherapeutics and glacial acetic acid is 1:30 ~ 1:50 in the said step (1); The gross mass of photosensitizer and Biodegradable high-molecular and the mass ratio of organic solvent are 1:19.
When Biodegradable polymer material was polylactic acid, organic solvent was the chloroform of volume ratio 7:3 and the mixed liquor of acetone in the said step (1); When Biodegradable polymer material was PETG, organic solvent was the trifluoroacetic acid of volume ratio 4:1 and the mixed liquor of dichloromethane; When Biodegradable polymer material was polyglycolic acid, organic solvent was a hexafluoroisopropanol; When Biodegradable polymer material was polycaprolactone, organic solvent was the trifluoroethanol of volume ratio 4:1 and the mixed liquor of water.
The technological parameter of the electrostatic spinning in the said step (2) is: apply voltage 15KV～25KV, receiving range 6cm～12cm, spinning fltting speed 0.3ml/h～1.50ml/h, spinning nozzle diameter 0.8mm.
In the homogeneous solution of the high polymer in the said step (2), miscible good between organic solvent, Biodegradable polymer material, anti-tumor photosensitizer, the chemotherapeutics, no chemical reaction.
Drug effect takes place, the laser irradiation competence exertion drug effect that photosensitizer will pass through specific wavelength when using in the desired loaded with anti-cancer medicine nano fibrous membrane of said step (2), the chemotherapeutics initial stage after operation.
Beneficial effect
(1) the present invention is carried the photo-dynamical medicine nanometer fibrous membrane as a kind of brand-new antitumor drug carrier; Can be after ocal resection; Medicament-carrying nano-fiber membrane is placed the tumor post-operation residual cavity, and chemotherapeutics discharges from slow-released carrier gradually, thereby keeps stable and effective concentration; The activation photosensitizer drug of laser, but non-toxic efficient, easy, place to go tumors remaining cell completely through certain wavelength in needs; Advantage such as have good biocompatibility, lasting medicine, can control reaches the purpose that prevents tumor recurrence, radical cure cancer; It is easy that this film is implanted the back treatment; Medicine carrying material meeting natural degradation has no side effect;
(2) cellular structure of nanofiber of the present invention helps organizing the exchange of ectendotrophy material and oxygen, promotes the histiocytic reparation in operation wound position, recovers normal function; Specific surface area that nanofiber is high and pore structure also help sticking, extend, breed and breaking up of cell; The micromolecule free radicals such as active oxygen that photosensitizer produces can so just can carry out optical dynamic therapy as required at any time through the loose structure diffusion of nanofiber in long-time, in time the tumor cell with recurrence kills:
(3) method for preparing of the present invention is simple to operate, and cost is low, has the excellent drug sustained release performance, has a extensive future.
The specific embodiment
Below in conjunction with specific embodiment, further set forth the present invention.Should be understood that these embodiment only to be used to the present invention is described and be not used in the restriction scope of the present invention.Should be understood that in addition those skilled in the art can do various changes or modification to the present invention after the content of having read the present invention's instruction, these equivalent form of values fall within the application's appended claims institute restricted portion equally.
That polylactic acid (PLLA) has is nontoxic, good biocompatibility, good mechanical property and advantage such as in organism, can degrade fully.Therefore, in the following instance, select for use this kind material as matrix, corresponding organic solvent selects for use chloroform to mix with acetone.Chemotherapeutics is selected 5-fluorouracil, and photosensitizer is selected the tetramethyl porphin, and two kinds of medicine mol ratios are 1:1, and the quality of medicine is 4% of a macromolecule matrix; The parameter that static spins directly influences the pattern of nanofiber, thereby influences its medicine carrying performance.
Embodiment 1
Weigh in the balance and get the 0.0133g 5-fluorouracil and be dissolved in the 0.5ml glacial acetic acid; And heating makes it whole dissolvings a little; Weigh in the balance and get 0.66g polylactic acid PLLA and 0.0133g tetramethyl porphin, it is dissolved in the 7ml chloroform, and seals bottleneck; Prevent solvent evaporates, on magnetic stirring apparatus, be stirred to dissolving fully.The glacial acetic acid solution of the 5-fluorouracil for preparing above adding then continues on magnetic stirring apparatus, to stir; The solution left standstill of mix homogeneously after 5 hours, is opened bottleneck, added 3ml acetone again, stir, spin high polymeric solution promptly getting static.Solution to obtaining carries out electrostatic spinning, and applying voltage is 15KV, and receiving range is 12cm, and the spinning fltting speed is 0.7ml/h, and the spinning nozzle diameter is 0.8mm.The gained nanofiber diameter is between the 350nm-1000nm.
Embodiment 2
Weigh in the balance and get the 0.0133g 5-fluorouracil and be dissolved in the 0.5ml glacial acetic acid; And heating makes it whole dissolvings a little; Weigh in the balance and get 0.66g polylactic acid PLLA and 0.0133g tetramethyl porphin, it is dissolved in the 7ml chloroform, and seals bottleneck; Prevent solvent evaporates, on magnetic stirring apparatus, be stirred to dissolving fully.The glacial acetic acid solution of the 5-fluorouracil for preparing above adding then continues on magnetic stirring apparatus, to stir; With the solution left standstill of mix homogeneously 5 hours, bottleneck is opened, add 3ml acetone again, stir, promptly get static and spin high polymeric solution.Solution to obtaining carries out electrostatic spinning, and applying voltage is 20KV, and receiving range is 12cm, and the spinning fltting speed is 0.8ml/h, and the spinning nozzle diameter is 0.8mm.The gained nanofiber diameter is between the 500nm-1500nm.
Embodiment 3
Weigh in the balance and get the 0.0133g 5-fluorouracil and be dissolved in the 0.5ml glacial acetic acid; And heating makes it whole dissolvings a little; Weigh in the balance and get 0.66g polylactic acid PLLA and 0.0133g tetramethyl porphin, it is dissolved in the 7ml chloroform, and seals bottleneck; Prevent solvent evaporates, on magnetic stirring apparatus, be stirred to dissolving fully.The glacial acetic acid solution of the 5-fluorouracil for preparing above adding then continues on magnetic stirring apparatus, to stir; The solution left standstill of mix homogeneously after 5 hours, is opened bottleneck, added 3ml acetone again, stir, promptly get static and spin high polymeric solution.Solution to obtaining carries out electrostatic spinning, and applying voltage is 15KV, and receiving range is 12cm, and the spinning fltting speed is 0.8ml/h, and the spinning nozzle diameter is 0.8mm.The gained nanofiber diameter is between the 400nm-1200nm.
Embodiment 4
Weigh in the balance and get the 0.0133g 5-fluorouracil and be dissolved in the 0.5ml glacial acetic acid; And heating makes it whole dissolvings a little, weighs in the balance and gets 0.66g polylactic acid PLLA and 0.0133g tetramethyl porphin, and it is dissolved in the 7ml chloroform; And seal bottleneck, prevent solvent evaporates.On magnetic stirring apparatus, be stirred to dissolving fully.The glacial acetic acid solution of the 5-fluorouracil for preparing above adding then continues on magnetic stirring apparatus, to stir; With the solution left standstill of mix homogeneously 5 hours, bottleneck is opened, add 3ml acetone again, stir, promptly get static and spin high polymeric solution.Solution to obtaining carries out electrostatic spinning, and applying voltage is 20KV, and receiving range is 12cm, and the spinning fltting speed is 0.7ml/h, and the spinning nozzle diameter is 0.8mm.The gained nanofiber diameter is between the 500nm-1500nm.
Claims (8)
1. loaded with anti-cancer medicine nano fibrous membrane; It is characterized in that: said nano fibrous membrane is made up of medicine carrying and matrix; Wherein, The photosensitizer and the chemotherapeutics that with the mol ratio are 1:1 ~ 2 are as the nano fibrous membrane medicine carrying, and with the matrix of Biodegradable polymer material as nano fibrous membrane, the medicine gross mass is 4% of a substrate quality.
2. a kind of loaded with anti-cancer medicine nano fibrous membrane according to claim 1 is characterized in that: said photosensitizer is Verteporfin or tetramethyl porphin.
3. a kind of loaded with anti-cancer medicine nano fibrous membrane according to claim 1 is characterized in that: said chemotherapeutics is 5-fluorouracil or methotrexate.
4. a kind of loaded with anti-cancer medicine nano fibrous membrane according to claim 1 is characterized in that: said Biodegradable polymer material is polylactic acid, PETG, polyglycolic acid or polycaprolactone, and molecular weight is 8W-30W.
5. the method for preparing of a loaded with anti-cancer medicine nano fibrous membrane as claimed in claim 1 comprises:
(1) chemotherapeutics is joined in the glacial acetic acid, heating makes medicine dissolution, obtains chemotherapeutics solution; Photosensitizer and Biodegradable polymer material are joined in the organic solvent, stir, add chemotherapeutics solution then, be mixed with high polymeric solution;
(2) above-mentioned high polymeric solution is carried out electrostatic spinning, volatilization organic solvent and glacial acetic acid make the loaded with anti-cancer medicine nano fibrous membrane.
6. the method for preparing of a kind of loaded with anti-cancer medicine nano fibrous membrane according to claim 5 is characterized in that: the mass ratio of chemotherapeutics and glacial acetic acid is 1:30 ~ 1:50 in the said step (1); The gross mass of photosensitizer and Biodegradable high-molecular and the mass ratio of organic solvent are 1:19.
7. the method for preparing of a kind of loaded with anti-cancer medicine nano fibrous membrane according to claim 5; It is characterized in that: when Biodegradable polymer material was polylactic acid, organic solvent was the chloroform of volume ratio 7:3 and the mixed liquor of acetone in the said step (1); When Biodegradable polymer material was PETG, organic solvent was the trifluoroacetic acid of volume ratio 4:1 and the mixed liquor of dichloromethane; When Biodegradable polymer material was polyglycolic acid, organic solvent was a hexafluoroisopropanol; When Biodegradable polymer material was polycaprolactone, organic solvent was the trifluoroethanol of volume ratio 4:1 and the mixed liquor of water.
8. the method for preparing of a kind of loaded with anti-cancer medicine nano fibrous membrane according to claim 5; It is characterized in that: the technological parameter of the electrostatic spinning in the said step (2) is: apply voltage 15KV～25KV; Receiving range 6cm～12cm; Spinning fltting speed 0.3ml/h～1.50ml/h, spinning nozzle diameter 0.8mm.
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Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN107308136A (en) * | 2017-07-05 | 2017-11-03 | 西南大学 | A kind of carrying anti-tumor medicine electrospinning micrometer fibers film and preparation method thereof |
| CN109432062A (en) * | 2018-11-16 | 2019-03-08 | 广东省医疗器械研究所 | A kind of load medicine electrospun fiber membrane and preparation method thereof |
| CN109453408A (en) * | 2018-11-16 | 2019-03-12 | 江南大学 | Antibacterial wound dressing and preparation method thereof |
| CN110180032A (en) * | 2019-06-12 | 2019-08-30 | 东华大学 | A kind of coaxial electrostatic spinning nano fiber scaffold and its preparation method and application carrying medicine controlled release |
| CN112546284A (en) * | 2020-12-22 | 2021-03-26 | 南通大学 | Degradable photothermal/chemotherapeutic synergistic anti-tumor fiber dressing |
| CN114831966A (en) * | 2022-04-08 | 2022-08-02 | 吉林医药学院 | Photothermal conversion nano composite material without toxic and side effects and preparation method and application thereof |
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| US20040058887A1 (en) * | 1999-08-31 | 2004-03-25 | Bowlin Gary L. | Electroprocessing in drug delivery and cell encapsulation |
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Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107308136A (en) * | 2017-07-05 | 2017-11-03 | 西南大学 | A kind of carrying anti-tumor medicine electrospinning micrometer fibers film and preparation method thereof |
| CN109432062A (en) * | 2018-11-16 | 2019-03-08 | 广东省医疗器械研究所 | A kind of load medicine electrospun fiber membrane and preparation method thereof |
| CN109453408A (en) * | 2018-11-16 | 2019-03-12 | 江南大学 | Antibacterial wound dressing and preparation method thereof |
| CN110180032A (en) * | 2019-06-12 | 2019-08-30 | 东华大学 | A kind of coaxial electrostatic spinning nano fiber scaffold and its preparation method and application carrying medicine controlled release |
| CN112546284A (en) * | 2020-12-22 | 2021-03-26 | 南通大学 | Degradable photothermal/chemotherapeutic synergistic anti-tumor fiber dressing |
| CN114831966A (en) * | 2022-04-08 | 2022-08-02 | 吉林医药学院 | Photothermal conversion nano composite material without toxic and side effects and preparation method and application thereof |
| CN114831966B (en) * | 2022-04-08 | 2024-04-19 | 吉林医药学院 | Photo-thermal conversion nanocomposite without toxic and side effects as well as preparation method and application thereof |
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