CN117618656A - Preparation method of porous hydroxyapatite microsphere containing PLGA drug-loaded particles, product and application thereof - Google Patents
Preparation method of porous hydroxyapatite microsphere containing PLGA drug-loaded particles, product and application thereof Download PDFInfo
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- CN117618656A CN117618656A CN202311741933.1A CN202311741933A CN117618656A CN 117618656 A CN117618656 A CN 117618656A CN 202311741933 A CN202311741933 A CN 202311741933A CN 117618656 A CN117618656 A CN 117618656A
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- 239000003814 drug Substances 0.000 title claims abstract description 55
- 229940079593 drug Drugs 0.000 title claims abstract description 53
- 239000004005 microsphere Substances 0.000 title claims abstract description 49
- 229920001606 poly(lactic acid-co-glycolic acid) Polymers 0.000 title claims abstract description 48
- 229910052588 hydroxylapatite Inorganic materials 0.000 title claims abstract description 30
- XYJRXVWERLGGKC-UHFFFAOYSA-D pentacalcium;hydroxide;triphosphate Chemical compound [OH-].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O XYJRXVWERLGGKC-UHFFFAOYSA-D 0.000 title claims abstract description 30
- 239000002245 particle Substances 0.000 title claims abstract description 29
- 238000002360 preparation method Methods 0.000 title claims abstract description 11
- 239000012071 phase Substances 0.000 claims abstract description 27
- CGMRCMMOCQYHAD-UHFFFAOYSA-J dicalcium hydroxide phosphate Chemical compound [OH-].[Ca++].[Ca++].[O-]P([O-])([O-])=O CGMRCMMOCQYHAD-UHFFFAOYSA-J 0.000 claims abstract description 20
- 239000004530 micro-emulsion Substances 0.000 claims abstract description 20
- 239000003921 oil Substances 0.000 claims abstract description 20
- 235000019198 oils Nutrition 0.000 claims abstract description 20
- 239000000839 emulsion Substances 0.000 claims abstract description 19
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 claims abstract description 19
- 239000008346 aqueous phase Substances 0.000 claims abstract description 14
- 238000004108 freeze drying Methods 0.000 claims abstract description 10
- 239000011812 mixed powder Substances 0.000 claims abstract description 10
- 238000005406 washing Methods 0.000 claims abstract description 10
- 238000002156 mixing Methods 0.000 claims abstract description 8
- 235000015112 vegetable and seed oil Nutrition 0.000 claims abstract description 4
- 239000008158 vegetable oil Substances 0.000 claims abstract description 4
- 239000000243 solution Substances 0.000 claims description 47
- 238000003756 stirring Methods 0.000 claims description 27
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 25
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 24
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 18
- 108010010803 Gelatin Proteins 0.000 claims description 12
- 239000008273 gelatin Substances 0.000 claims description 12
- 229920000159 gelatin Polymers 0.000 claims description 12
- 235000019322 gelatine Nutrition 0.000 claims description 12
- 235000011852 gelatine desserts Nutrition 0.000 claims description 12
- SXRSQZLOMIGNAQ-UHFFFAOYSA-N Glutaraldehyde Chemical compound O=CCCCC=O SXRSQZLOMIGNAQ-UHFFFAOYSA-N 0.000 claims description 9
- 229930012538 Paclitaxel Natural products 0.000 claims description 9
- 239000004372 Polyvinyl alcohol Substances 0.000 claims description 9
- 238000000034 method Methods 0.000 claims description 9
- 229920002113 octoxynol Polymers 0.000 claims description 9
- 229960001592 paclitaxel Drugs 0.000 claims description 9
- 239000002504 physiological saline solution Substances 0.000 claims description 9
- 229920002451 polyvinyl alcohol Polymers 0.000 claims description 9
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 claims description 9
- NWGKJDSIEKMTRX-AAZCQSIUSA-N Sorbitan monooleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O NWGKJDSIEKMTRX-AAZCQSIUSA-N 0.000 claims description 8
- 239000011859 microparticle Substances 0.000 claims description 8
- 238000006243 chemical reaction Methods 0.000 claims description 6
- 239000000463 material Substances 0.000 claims description 6
- 235000008390 olive oil Nutrition 0.000 claims description 6
- 239000004006 olive oil Substances 0.000 claims description 6
- XRASPMIURGNCCH-UHFFFAOYSA-N zoledronic acid Chemical compound OP(=O)(O)C(P(O)(O)=O)(O)CN1C=CN=C1 XRASPMIURGNCCH-UHFFFAOYSA-N 0.000 claims description 5
- 229960004276 zoledronic acid Drugs 0.000 claims description 5
- 239000007864 aqueous solution Substances 0.000 claims description 4
- 239000007788 liquid Substances 0.000 claims description 4
- 239000003504 photosensitizing agent Substances 0.000 claims description 4
- 239000004094 surface-active agent Substances 0.000 claims description 4
- 239000011268 mixed slurry Substances 0.000 claims description 3
- 229920001213 Polysorbate 20 Polymers 0.000 claims description 2
- 229920001214 Polysorbate 60 Polymers 0.000 claims description 2
- 230000000259 anti-tumor effect Effects 0.000 claims description 2
- 239000002639 bone cement Substances 0.000 claims description 2
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 claims description 2
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 claims description 2
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 claims description 2
- 229920000053 polysorbate 80 Polymers 0.000 claims description 2
- 230000003115 biocidal effect Effects 0.000 claims 1
- 230000000694 effects Effects 0.000 abstract description 6
- 238000011049 filling Methods 0.000 abstract description 4
- 231100000331 toxic Toxicity 0.000 abstract description 3
- 230000002588 toxic effect Effects 0.000 abstract description 3
- 230000015556 catabolic process Effects 0.000 abstract description 2
- 238000006731 degradation reaction Methods 0.000 abstract description 2
- 238000009792 diffusion process Methods 0.000 abstract description 2
- 238000004945 emulsification Methods 0.000 abstract description 2
- 239000002002 slurry Substances 0.000 abstract 1
- 210000000988 bone and bone Anatomy 0.000 description 4
- 230000007547 defect Effects 0.000 description 3
- 210000001519 tissue Anatomy 0.000 description 2
- 208000020084 Bone disease Diseases 0.000 description 1
- 208000018084 Bone neoplasm Diseases 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 206010031252 Osteomyelitis Diseases 0.000 description 1
- 208000001132 Osteoporosis Diseases 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 238000013329 compounding Methods 0.000 description 1
- 238000002316 cosmetic surgery Methods 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 238000001000 micrograph Methods 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 229920000728 polyester Polymers 0.000 description 1
- 230000003014 reinforcing effect Effects 0.000 description 1
- 210000004872 soft tissue Anatomy 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
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- Medicinal Preparation (AREA)
Abstract
The invention relates to a preparation method of porous hydroxyapatite microspheres containing PLGA drug-loaded particles, a product and application thereof, preparing an oil phase solution, preparing an aqueous phase solution, and adding the oil phase solution into the aqueous phase solution to obtain W/O type microemulsion; adding alpha-TCP and hydroxyapatite mixed powder into the microemulsion, and adding the slurry after uniform mixing into vegetable oil to obtain O/W type emulsion; and (3) centrifugally washing, freeze-drying to obtain the porous hydroxyapatite microsphere containing PLGA drug-loaded particles. The invention prepares the micron-sized hydroxyapatite microsphere containing PLGA drug-loaded particles by using an emulsion method, can be used for tissue filling repair and drug long-acting delivery, wraps the PLGA microsphere with the fat-soluble drug, releases the drug by slow diffusion and microsphere degradation, prolongs the release time of the drug, reduces the toxic and side effects generated by drug burst release, and achieves the effect of long-acting treatment.
Description
Technical Field
The invention relates to a method in the technical field of biomedical materials, in particular to a preparation method of porous hydroxyapatite microspheres containing PLGA drug-loaded particles, a product and application thereof.
Background
Hydroxyapatite is a main inorganic component constituting bones and teeth of a human body, has the advantages of good bioactivity, biocompatibility, bone conductivity and the like, does not generate inflammatory reaction after being placed in a body, can be biodegraded, and is widely applied to clinical tissue engineering repair of orthopaedics, dentistry, plastic surgery and the like. The porous hydroxyapatite microsphere is a microsphere hydroxyapatite particle, the main component is hydroxyapatite, micropores of the hydroxyapatite microsphere are beneficial to cell growth, nutrient transmission and metabolite discharge, and the hydroxyapatite microsphere can be used for repairing or filling bone defects and repairing or reinforcing soft tissues caused by various reasons by compounding gel or solidifying liquid and the like.
In the treatment of bone defects caused by bone diseases such as osteomyelitis, bone tumors and osteoporosis, continuous drug treatment for several months is often required to complete defect healing, and for some traditional drug-loading methods, such as directly mixing drugs in porous microspheres, the long-acting slow-release requirement cannot be met. In addition, some fat-soluble drugs such as taxol, zoledronic acid and the like can generate certain toxic and side effects when being released too quickly in vivo, and the treatment effect is affected. The PLGA microsphere is a polyester material which can be slowly degraded in water, and can prolong the slow release period of the medicine. Against the background, the invention provides a preparation method of porous hydroxyapatite microspheres containing PLGA drug-loaded particles, which is used for preparing degradable filling materials with long-term drug release capability.
Disclosure of Invention
The invention aims to provide a preparation method of porous hydroxyapatite microspheres containing PLGA drug-loaded particles.
Still another object of the present invention is: the porous hydroxyapatite microsphere product containing PLGA drug-loaded microparticles prepared by the method is provided.
Yet another object of the present invention is: there is provided the use of the above product.
The invention aims at realizing the following scheme:
the invention aims to realize a preparation method of porous hydroxyapatite microspheres containing PLGA drug-loaded particles by the following technical scheme, which comprises the following steps:
(1) Preparation of PLGA drug-loaded microparticles: dissolving a fat-soluble drug and PLGA in methylene dichloride to obtain an oil phase solution, preparing an aqueous solution containing 5-10% (W/v) of gelatin and 1-2% (W/v) of polyvinyl alcohol as an aqueous phase solution, adding the oil phase solution into the aqueous phase solution according to the volume ratio of 1:10, and stirring at 900rpm for 2 hours at 60 ℃ to obtain W/O type microemulsion;
(2) Adding alpha-TCP mixed powder with the mass fraction of 1-5% of hydroxyapatite into the microemulsion of the step (1) according to the solid-to-liquid ratio of 1.2-1.5mL/g, adding the uniformly mixed slurry into vegetable oil with the surfactant at the temperature of 60 ℃ according to the volume ratio of 1:10-1:100 to obtain O/W emulsion, and continuously stirring until the alpha-TCP is solidified;
(3) Transferring the emulsion into ice bath, adding physiological saline containing 0.1% triton-X as demulsifier, adding glutaraldehyde solution to crosslink gelatin, and stirring for 2 hr. Centrifugally extracting the microspheres, respectively washing the microspheres with ethanol and water for 3 times, and freeze-drying the microspheres to obtain the porous hydroxyapatite microspheres containing PLGA drug-loaded particles.
The preparation method of the aqueous phase solution in the step (1) is that the aqueous phase solution is stirred and dissolved in a water bath at 60 ℃.
The liposoluble medicine in step (1) comprises antitumor, photosensitizer, antibiotics such as paclitaxel, zoledronic acid, and IR780.
The surfactant in the step (2) is one or more of Tween 20, tween 60, tween 80 and span 80.
The invention provides a porous hydroxyapatite microsphere containing PLGA drug-loaded particles, which is prepared by any one of the methods.
The invention provides an application of porous hydroxyapatite microspheres containing PLGA drug-loaded microparticles in preparing materials required by drug-sustained-release bone cement according to claim 5.
Preparing a dichloromethane solution containing fat-soluble drugs and PLGA as an oil phase solution, preparing an aqueous solution containing polyvinyl alcohol and gelatin as an aqueous phase solution, adding the oil phase solution into the aqueous phase solution, and stirring at a high speed at 60 ℃ for 2 hours to obtain W/O type microemulsion; adding alpha-TCP and hydroxyapatite mixed powder into the microemulsion according to the solid-to-liquid ratio of 1.2-1.5mL/g, adding the uniformly mixed slurry into vegetable oil at 60 ℃ to obtain O/W type emulsion, and continuously stirring until the alpha-TCP is solidified; transferring the emulsion into ice bath, adding physiological saline containing 0.1% triton-X as demulsifier, adding glutaraldehyde solution to crosslink gelatin, and stirring for 2 hr; centrifugally extracting the microspheres, respectively washing the microspheres with ethanol and water for 3 times, and freeze-drying the microspheres to obtain the porous hydroxyapatite microspheres containing PLGA drug-loaded particles.
The invention has the advantages that:
the emulsion method for preparing the micro-scale hydroxyapatite microsphere containing PLGA drug-loaded particles can be used for tissue filling repair and drug long-acting delivery, expands the application range of the material, wraps the PLGA microsphere with the liposoluble drug, releases the drug by slow diffusion and microsphere degradation, prolongs the release time of the drug, reduces the toxic and side effects generated by drug burst release, and achieves the effect of long-acting treatment.
Drawings
FIG. 1 is a scanning electron microscope image of porous hydroxyapatite microspheres containing PLGA-loaded microparticles prepared in example 1.
Detailed Description
The following examples are given with the invention as defined by the detailed description and the specific procedures, but the scope of the invention is not limited to the following examples.
Example 1
A porous hydroxyapatite microsphere containing PLGA drug-loaded particles is prepared by the following steps:
(1) 100mg of paclitaxel and 100mg of PLGA are dissolved in 1mL of dichloromethane to obtain an oil phase solution; 0.5g of gelatin and 0.1g of polyvinyl alcohol were dissolved in 10mL of pure water as an aqueous phase solution; adding the oil phase solution into the water phase solution, and stirring at a high speed of 900rpm at 60 ℃ for 2 hours to obtain W/O type microemulsion;
(2) Adding 0.32g of hydroxyapatite and 7.68g of alpha-TCP mixed powder into the microemulsion, uniformly mixing, adding into 300mL of olive oil containing 3g of span-80 to obtain O/W emulsion, and continuously stirring until the alpha-TCP is solidified;
(3) Transferring the emulsion into ice bath, adding 300mL of physiological saline containing 0.1% triton-X as demulsifier, simultaneously adding 500 mu L of 1% (w/v) glutaraldehyde solution, and continuously stirring for 2h; and after the reaction is finished, centrifugally extracting the microspheres, respectively washing the microspheres with ethanol and water for 3 times, and freeze-drying the microspheres to obtain the porous hydroxyapatite microspheres containing PLGA drug-loaded particles.
The scanning electron microscope picture of the prepared porous hydroxyapatite microsphere containing PLGA drug-loaded particles is shown in figure 1.
Example 2
A porous hydroxyapatite microsphere containing PLGA drug-loaded particles is prepared by the following steps:
(1) 200mg of paclitaxel and 100mg of PLGA are dissolved in 1mL of dichloromethane to obtain an oil phase solution; 0.5g of gelatin and 0.1g of polyvinyl alcohol were dissolved in 10mL of pure water as an aqueous phase solution; adding the oil phase solution into the water phase solution, and stirring at a high speed of 900rpm at 60 ℃ for 2 hours to obtain W/O type microemulsion;
(2) Adding 0.14g of hydroxyapatite and 6.86g of alpha-TCP mixed powder into the microemulsion, uniformly mixing, adding into 100mL of olive oil containing 1g of span-80 to obtain O/W emulsion, and continuously stirring until the alpha-TCP is solidified;
(3) Transferring the emulsion into ice bath, adding 100mL physiological saline containing 0.1% triton-X as demulsifier, simultaneously adding 500 μL 1% (w/v) glutaraldehyde solution, and stirring for 2 hr; and after the reaction is finished, centrifugally extracting the microspheres, respectively washing the microspheres with ethanol and water for 3 times, and freeze-drying the microspheres to obtain the porous hydroxyapatite microspheres containing PLGA drug-loaded particles.
Example 3
A porous hydroxyapatite microsphere containing PLGA drug-loaded particles, which is prepared by replacing zoledronic acid with paclitaxel of example 1, comprising the following steps:
(1) 100mg zoledronic acid and 100mg PLGA are dissolved in 1mL of methylene dichloride to obtain an oil phase solution; 0.5g of gelatin and 0.1g of polyvinyl alcohol were dissolved in 10mL of pure water as an aqueous phase solution; adding the oil phase solution into the water phase solution, and stirring at a high speed of 900rpm at 60 ℃ for 2 hours to obtain W/O type microemulsion;
(2) Adding 0.32g of hydroxyapatite and 7.68g of alpha-TCP mixed powder into the microemulsion, uniformly mixing, adding into 300mL of olive oil containing 3g of span-80 to obtain O/W emulsion, and continuously stirring until the alpha-TCP is solidified;
(2) Transferring the emulsion into ice bath, adding 300mL of physiological saline containing 0.1% triton-X as demulsifier, simultaneously adding 500 mu L of 1% (w/v) glutaraldehyde solution, and continuously stirring for 2h; and after the reaction is finished, centrifugally extracting the microspheres, respectively washing the microspheres with ethanol and water for 3 times, and freeze-drying the microspheres to obtain the porous hydroxyapatite microspheres containing PLGA drug-loaded particles.
Example 4
A porous hydroxyapatite microsphere containing PLGA drug-loaded microparticles, which is prepared by substituting photosensitizer IR780 with paclitaxel of example 1, comprises the following steps:
(1) 100mg of photosensitizer IR780 and 100mg of PLGA are dissolved in 1mL of dichloromethane to obtain an oil phase solution; 0.5g of gelatin and 0.1g of polyvinyl alcohol were dissolved in 10mL of pure water as an aqueous phase solution; adding the oil phase solution into the water phase solution, and stirring at a high speed of 900rpm at 60 ℃ for 2 hours to obtain W/O type microemulsion;
(2) Adding 0.32g of hydroxyapatite and 7.68g of alpha-TCP mixed powder into the microemulsion, uniformly mixing, adding into 300mL of olive oil containing 3g of span-80 to obtain O/W emulsion, and continuously stirring until the alpha-TCP is solidified;
(2) Transferring the emulsion into ice bath, adding 300mL of physiological saline containing 0.1% triton-X as demulsifier, simultaneously adding 500 mu L of 1% (w/v) glutaraldehyde solution, and continuously stirring for 2h; and after the reaction is finished, centrifugally extracting the microspheres, respectively washing the microspheres with ethanol and water for 3 times, and freeze-drying the microspheres to obtain the porous hydroxyapatite microspheres containing PLGA drug-loaded particles.
Claims (7)
1. The preparation method of the porous hydroxyapatite microsphere containing PLGA drug-loaded particles is characterized by comprising the following steps:
(1) Preparation of PLGA drug-loaded microparticles:
dissolving a fat-soluble drug and PLGA in dichloromethane to obtain an oil phase solution; preparing an aqueous solution containing 5-10% (w/v) of gelatin and 1-2% (w/v) of polyvinyl alcohol as an aqueous solution; adding the oil phase solution into the water phase solution according to the volume ratio of 1:10, and stirring at a high speed of 900rpm at 60 ℃ for 2 hours to obtain W/O type microemulsion;
(2) Adding alpha-TCP mixed powder with the mass fraction of 1-5% of hydroxyapatite into the microemulsion obtained in the step (1) according to the solid-to-liquid ratio of 1.2-1.5mL/g, adding the uniformly mixed slurry into vegetable oil containing a surfactant at the temperature of 60 ℃ according to the volume ratio of 1:10-1:100 to obtain O/W emulsion, and continuously stirring until the alpha-TCP is solidified;
(3) Transferring the emulsion obtained in the step (2) into ice bath, adding physiological saline containing 0.1% triton-X as demulsifier, adding glutaraldehyde solution to further crosslink gelatin, continuously stirring for 2h, centrifugally extracting microspheres, respectively washing with ethanol and water for 3 times, and freeze-drying to obtain porous hydroxyapatite microspheres containing PLGA drug-loaded particles.
2. The method of claim 1, wherein the liposoluble drug in step (1) comprises antitumor, photosensitizer, antibiotic, such as paclitaxel, zoledronic acid, and IR780.
3. The method for preparing porous hydroxyapatite microspheres containing PLGA drug-loaded microparticles according to claim 1, wherein the surfactant in step (2) is one or more of tween 20, tween 60, tween 80 and span 80.
4. A method of preparing porous hydroxyapatite microspheres containing PLGA-loaded drug particles according to any one of claims 1 to 3, comprising the steps of:
(1) 100mg of paclitaxel and 100mg of PLGA are dissolved in 1mL of dichloromethane to obtain an oil phase solution; 0.5g of gelatin and 0.1g of polyvinyl alcohol were dissolved in 10mL of pure water as an aqueous phase solution; adding the oil phase solution into the water phase solution, and stirring at a high speed of 900rpm at 60 ℃ for 2 hours to obtain W/O type microemulsion;
(2) Adding 0.32g of hydroxyapatite and 7.68g of alpha-TCP mixed powder into the microemulsion, uniformly mixing, adding into 300mL of olive oil containing 3g of span-80 to obtain O/W emulsion, and continuously stirring until the alpha-TCP is solidified;
(3) Transferring the emulsion into ice bath, adding 300mL of physiological saline containing 0.1% triton-X as demulsifier, simultaneously adding 500 mu L of 1% (w/v) glutaraldehyde solution, and continuously stirring for 2h; and after the reaction is finished, centrifugally extracting the microspheres, respectively washing the microspheres with ethanol and water for 3 times, and freeze-drying the microspheres to obtain the porous hydroxyapatite microspheres containing PLGA drug-loaded particles.
5. A method of preparing porous hydroxyapatite microspheres containing PLGA-loaded drug particles according to any one of claims 1 to 3, comprising the steps of:
(1) 200mg of paclitaxel and 100mg of PLGA are dissolved in 1mL of dichloromethane to obtain an oil phase solution; 0.5g of gelatin and 0.1g of polyvinyl alcohol were dissolved in 10mL of pure water as an aqueous phase solution; adding the oil phase solution into the water phase solution, and stirring at a high speed of 900rpm at 60 ℃ for 2 hours to obtain W/O type microemulsion;
(2) Adding 0.14g of hydroxyapatite and 6.86g of alpha-TCP mixed powder into the microemulsion, uniformly mixing, adding into 100mL of olive oil containing 1g of span-80 to obtain O/W emulsion, and continuously stirring until the alpha-TCP is solidified;
(3) Transferring the emulsion into ice bath, adding 100mL physiological saline containing 0.1% triton-X as demulsifier, simultaneously adding 500 μL 1% (w/v) glutaraldehyde solution, and stirring for 2 hr; and after the reaction is finished, centrifugally extracting the microspheres, respectively washing the microspheres with ethanol and water for 3 times, and freeze-drying the microspheres to obtain the porous hydroxyapatite microspheres containing PLGA drug-loaded particles.
6. A porous hydroxyapatite microsphere containing PLGA drug-loaded microparticles, characterized in that it is prepared according to the method of any one of claims 1-5.
7. Use of the porous hydroxyapatite microspheres containing PLGA-loaded drug particles according to claim 6 for preparing a material for a drug-eluting bone cement.
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