The utilization microemulsion method prepares the method for magnetic silica medicine-carried microsphere in the Oleum Gossypii semen
Technical field
The invention belongs to utilization microemulsion method in the preparation method field, particularly Oleum Gossypii semen of magnetic nanometer particles carrier and prepare the method for magnetic silica medicine-carried microsphere.
Background technology
As a kind of phyllins, photosensitizer C.I. Natural Red 8-18 has many-sided biological activitys such as promoting organization healing, antiulcer and protects the liver.Because the existence of porphyrin ring, it can discern and be enriched in sick cell, the local high concentration that produces, bring into play its effect, under photodynamics, produce active oxygen, make the amino acid side chain oxidation, cause the protein oxidation fracture rotten, finally make sick cell forfeiture self-regulating function and apoptosis, therefore can be used for photodynamic therapy (Photodynamic Therapy, PDT).The CHLOROPHYLLINE catabolite has ideal action spectrum, high red light district absorptance, and eliminate characteristics such as rapid in vivo, as PDT medicine and synthetic precursor application promise in clinical practice is arranged.
Photodynamic therapy now has been applied to treat multiple disease, but because most of photosensitizer are hydrophobic drugs, in vivo can not stable existence in the water environment, therefore, the targeting that strengthens the stability of photosensitizer in aqueous solution and improve photosensitizer more and more causes people's attention.In view of magnetic nanometer particles in recent years at the (J.Magn.Magn.Mater.2001 more and more widely of the application aspect the drug delivery, 225,21-29), photodynamics medicine and magnetic nanometer particles combine also becomes the focus (J.Magn.Magn.Mater.2005 of research with the targeting that improves photosensitizer, 289,476-479).Nano silicon is as the sophisticated nonmetallic materials of a kind of research, has better biocompatibility, preparation technology's flow process is simple, and good stability, can not produce qualitative change owing to the variation of environment, parcel silicon dioxide can effectively strengthen the stability of photosensitizer in aqueous solution on the surface of magnetic drug-carrying microsphere.Roy etc. have reported the preparation method that silicon dioxide and photodynamics medicine (HPPH) combine, the silica medicine-carried microsphere size that makes about 30nm, and have preferably photodynamic effect (J.Am.Chem.Soc.2003,125,7860-7865).Cinteza etc. have reported with polymer coated magnetic nanoparticle and photodynamics medicine methylene blues such as amphipathic Macrogol 2000 distearyl phospholipid ethanolamine, also obtained preferably effect (MOL PHARMACOL.2006,3,415-423).In sum, prove absolutely that magnetic drug-carrying microsphere complex has potential development prospect in the photodynamics application facet.
Summary of the invention
The purpose of this invention is to provide a kind of method of utilizing microemulsion method to prepare magnetic silica medicine-carried microsphere in Oleum Gossypii semen, this method is to be prepared from microemulsion method in Oleum Gossypii semen, generates SiO with ethyl orthosilicate as the silicon source
2To Fe
3O
4Coat with photodynamics medicine C.I. Natural Red 8-18.Technology of the present invention is simple, can finish under the room temperature, and cost of material is low, is widely used in multiple photodynamics medicine.
A kind of method of utilizing microemulsion method to prepare magnetic silica medicine-carried microsphere in Oleum Gossypii semen of the present invention comprises the following steps:
(1) under the room temperature that dehydrated alcohol and water is mixed, obtain settled solution;
(2) in the solution of step (1), add ferroso-ferric oxide and drug solution respectively, stirred 5-15 minute, add cross-linking agent silane coupler (3-sulfydryl propyl group) trimethoxy silane (MPS) then, ultrasonic 5-15 minute;
(3) in the system of step (2), add ammonia, again whole reaction system is inserted in the Oleum Gossypii semen, stirred 0.5-1 hour after ultrasonic 5-15 minute;
(4) in the solution of step (3), add silicon source ethyl orthosilicate (TEOS), stir and obtained sample solution in 16-20 hour;
(5) sample solution centrifugalize is cleaned with petroleum ether, dehydrated alcohol successively, and vacuum drying gets magnetic silica medicine-carried microsphere nano granule.
The volume ratio of described dehydrated alcohol and water is 1: 2;
Described ferroso-ferric oxide is the nano-particle with classical coprecipitation preparation;
Described drug solution is that concentration is the photodynamics medicine C.I. Natural Red 8-18 of 15mM;
The concentration of described ammonia is 27%;
The mol ratio of described silicon source and ferroso-ferric oxide is 1: 17;
Beneficial effect of the present invention:
(1) cost of material of the present invention is low, technology is simple, can finish at normal temperatures;
(2) size of Zhi Bei photo-dynamical medicine nanometer magnetic carrier is evenly distributed at 20-30nm, good dispersion, and good biocompatibility, magnetic responsiveness is strong, and the photodynamics medicine can well play a role, and can be widely used in multiple photodynamics preparation of drug carriers.
Description of drawings
Fig. 1 is the main technique flow chart that the utilization microemulsion method prepares the method for magnetic silica medicine-carried microsphere in Oleum Gossypii semen;
Fig. 2 is the transmission electron microscope photo that the utilization microemulsion method prepares magnetic silica medicine-carried microsphere in Oleum Gossypii semen;
Fig. 3 is the uv-spectrogram that causes right-nitrosodimethylaniline (RNO) decoloring reaction along with the variation of laser irradiation time.
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 and limit the scope of the invention.Should be understood that in addition those skilled in the art can make various changes or modifications 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.
Embodiment 1
(1) under the room temperature that dehydrated alcohol 0.5mL and deionized water 1mL is mixed, obtain settled solution;
(2) in the solution of step (1), add ferroso-ferric oxide 0.0009g and C.I. Natural Red 8-18 drug solution 300 μ L (concentration is 15m M) respectively, stirred 15 minutes, add cross-linking agent MPS 10 μ L then, supersound process 15 minutes;
(3) in the system of step (2), add ammonia 1mL, again whole reaction system is inserted in the 15mL Oleum Gossypii semen, stirred 1 hour after ultrasonic 15 minutes;
(4) in the solution of step (3), add ethyl orthosilicate 10 μ L, stir and obtained sample in 20 hours;
(5) sample solution centrifuge centrifugalize separates cleaning with petroleum ether, and then cleans with dehydrated alcohol, and vacuum drying gets magnetic silica medicine-carried microsphere nano granule.Its transmission electron microscope photo is seen accompanying drawing 2, and nano-particle shows as Δ OD along with the variation of laser irradiation time causes the uv-spectrogram of RNO decoloring reaction to see accompanying drawing 3
440Increase with light application time increases, and judges the release of singlet oxygen thus.
Embodiment 2
(1) under the room temperature that dehydrated alcohol 0.5mL and deionized water 1mL is mixed, obtain settled solution;
(2) in the solution of step (1), add ferroso-ferric oxide aqueous solution 160 μ L (wherein containing ferroso-ferric oxide 0.0009g) and C.I. Natural Red 8-18 drug solution 500 μ L (concentration is 15mM) respectively, stirred 15 minutes, add cross-linking agent MPS 10 μ L then, supersound process 15 minutes;
(3) in the system of step (2), add ammonia 1mL, again whole reaction system is inserted in the 20mL Oleum Gossypii semen, stirred 1 hour after ultrasonic 15 minutes;
(4) in the solution of step (3), add ethyl orthosilicate 10 μ L, stir and obtained sample in 20 hours;
(5) sample solution centrifuge centrifugalize separates cleaning with petroleum ether, and then cleans with dehydrated alcohol, and vacuum drying gets magnetic silica medicine-carried microsphere nano granule.
Embodiment 3
(1) under the room temperature that dehydrated alcohol 0.5mL and deionized water 1mL is mixed, obtain settled solution;
(2) in the solution of step (1), add ferroso-ferric oxide aqueous solution 160 μ L (wherein containing ferroso-ferric oxide 0.0009g) and C.I. Natural Red 8-18 drug solution 200 μ L (concentration is 30mM) respectively, stirred 15 minutes, add cross-linking agent MPS 10 μ L then, supersound process 15 minutes;
(3) in the system of step (2), add ammonia 1mL, again whole reaction system is inserted in the 20mL Oleum Gossypii semen, stirred 1 hour after ultrasonic 15 minutes;
(4) in the solution of step (3), add ethyl orthosilicate 10 μ L, stir and obtained sample in 20 hours;
(5) sample solution centrifuge centrifugalize separates cleaning with petroleum ether, and then cleans with dehydrated alcohol, and vacuum drying gets magnetic silica medicine-carried microsphere nano granule.