KR101137886B1 - Image diagnostic drug delivery carrier using porous silicon particles and manufacturing method thereof - Google Patents

Abstract

The present invention relates to an imaging diagnostic drug carrier using porous silicon particles and a method of manufacturing the same.

The imaging diagnostic drug carrier of the present invention uses a biocompatible silicone material, thermally oxidizes the surface of the multilayer porous silicon film prepared by an electrochemical etching method, and easily adheres the drug to the surface thereof, and then ultrasonically pulverizes the porous material. As silicon particles, the pulverized particles retain the optical properties of the porous silicon and, as provided in the form of particles, can increase the selectivity to micromolecules. Furthermore, the imaging diagnostic drug carrier of the present invention can control the release rate due to hydrolysis of the drug according to the pH of the buffer solution, and can monitor in real time the degree of drug release from the porous silicon particles through the amplification process of the signal In addition, since the amount of drug released can be predicted, it is particularly useful as an image diagnosis drug carrier in a drug delivery system.

Porous Silicon Particles, Image Diagnosis, Drug Carrier, Drug Delivery System

Description

IMAGE DIAGNOSTIC DRUG DELIVERY CARRIER USING POROUS SILICON PARTICLES AND MANUFACTURING METHOD THEREOF}

The present invention relates to an image diagnosis drug carrier using porous silicon particles and a method of manufacturing the same, and more particularly, to thermally oxidize the surface of a multilayer porous silicon film prepared by an electrochemical etching method, After the easy fixation, the present invention relates to an image diagnostic drug carrier using ultrasonically pulverized porous silicon particles and a method of manufacturing the same.

Drug delivery system (hereinafter referred to as "DDS") technology refers to a medical technology that can efficiently deliver the required amount of drugs by minimizing the side effects of existing drugs, maximizing efficacy and effectiveness.

This technology, which saves the cost and time required to develop new drugs, has recently become one of the cutting-edge technologies that combines with nanotechnology to create new added value in the pharmaceutical industry. The company has devoted itself to developing drug delivery system technology along with the development of new drugs with companies and companies.

Since the introduction of material patents in 1987, Korea has made certain achievements in the development of DDS technology by establishing a comprehensive research system in pharmaceutical companies, academia and research institutes in order to create new added value in the pharmaceutical field.

Recently, research has been published to develop drug delivery microchips that can maintain a long-term efficacy with a single dose, which can lead to major innovations in existing medication practices such as anticancer drugs and hormonal drugs. As such, the development of DDS technology requires the development of customized drug delivery materials that can be dosed at the time and place needed to meet the needs of patients and consumers.

Accordingly, the present inventors searched for a novel drug delivery material material, and as a result of setting the most stable silicon material in the living body, and trying to solve the problem is extremely limited and difficult when the conventional silicon material synthesis, electrochemical etching Method to prepare a multilayer porous silicon film, thermally oxidize the surface thereof to obtain a biocompatible porous silicon material, fix the drug on the surface, and then apply the pulverized porous silicon particles as an image diagnostic drug carrier. By confirming, the present invention was completed.

It is an object of the present invention to provide an imaging diagnostic drug carrier using a biocompatible silicone material.

Another object of the present invention is to maintain the optical properties of the electrochemically etched porous silicon, and to fix the drug on the oxidized surface of the porous silicon particles, and then to prepare a method for producing an image diagnostic drug carrier consisting of pulverized porous silicon particles To provide.

In order to achieve the above object, the present invention is a multi-layer porous silicon film prepared by the electrochemical etching method is thermally oxidized, the target drug is fixed on the oxidized porous silicon dioxide (hereinafter referred to as "PSD") film surface It is then crushed to provide an imaging diagnostic drug carrier characterized by porous silicon dioxide particles surface-induced with a drug.

The porous silicon dioxide particles surface-induced with the drug of the present invention are hydrolyzed under the condition of pH 4-9 to control the release rate of the drug.

In this case, the surface-induced porous silicon dioxide particle size of the drug of the present invention is pulverized from several microns to several nano-size particle size.

In the present invention, the porous silicon dioxide (PSD) film is treated for 1 to 3 hours at 300 ~ 1200 ℃ temperature conditions and the surface is thermally oxidized to -Si-OH, the target drug used in the drug carrier of the present invention is Any drug that can bind to the oxidized surface is applicable without particular limitation, but in the present invention, camptothecin (hereinafter referred to as "CPT") is used.

The present invention provides a method for producing an imaging diagnostic drug delivery. More specifically,

1) preparing a multilayer porous silicon by etching the silicon wafer by an electrochemical method, 2) separating the multilayer porous silicon into a porous silicon film from the silicon wafer, 3) the temperature of the porous silicon film 300 ~ 1200 ℃ Forming a porous silicon dioxide (PSD) film whose surface is oxidized by heating for 1 to 3 hours under the condition; and 4) pulverizing the surface of the oxidized porous silicon dioxide (PSD) film by induction with a target drug, followed by grinding. In the process to prepare a porous silicon dioxide (PSD) particles.

In the manufacturing method of the present invention, the multilayer porous silicon of step 1) is 120-200 mA / cm 2 of central current value, and is electrically etched using 2 to 30 sinusoidal mixed currents, and then, 2 to 400 to 2000 nm. To 30 multiple reflection peaks.

In addition, the multilayer porous silicon of step 1) is a rectangular wave condition of alternating current of 1 to 50 mA / cm ² for 1 to 200 seconds and 10 to 500 mA / cm ² for 1 to 30 seconds. The present center current and the current higher than the center current are each performed twice or more, and those having 2 to 30 multiple reflection peaks (DBR multiple peaks) at 400 to 2000 nm are used.

In addition, the ground porous silicon dioxide (PSD) particles of step 4) is preferably ultrasonically ground.

According to the present invention, it is possible to provide an image diagnosis drug carrier using a biocompatible silicone material.

The imaging diagnostic drug carrier of the present invention manufactures a multilayer porous silicon film by an electrochemical etching method, thermally oxidizes the surface thereof to obtain a biocompatible porous silicon material, and fixes the drug on the surface thereof, followed by pulverizing the porous silicon film. The particles retain the optical properties of porous silicon and provide them in the form of milled particles.

Hereinafter, the present invention will be described in detail.

The present invention is a multi-layer porous silicon film prepared by the electrochemical etching method is thermally oxidized, the target drug is fixed on the surface of the oxidized porous silicon dioxide (PSD) film and then pulverized, the surface-derived porous silicon dioxide particles with a drug It provides a drug delivery carrier characterized by.

The silicon material used as the image diagnosis drug carrier material of the present invention is an optically encoded porous silicon prepared by electrochemical etching with a sine wave current, and can be synthesized by Equation 1 below.

(A is the amplitude, k is the frequency (Hz), t is time, and B is the median of the waveform.)

The multilayer porous silicon (PSi) of the present invention has a center current of 120 to 200 mA / cm 2, and is electrochemically etched using 2 to 30 sinusoidal mixed currents, and 2 to 30 particles at 400 to 2000 nm. Multi-layer porous silicon having a multiple reflection peak is used.

Multilayer porous silicon (PSi) can be fabricated by controlling the waveform and etching conditions of the sine wave. The advantage of multilayer porous silicon is that it is reflected from the porous silicon when it is Fourier transformed to the waveform using the sine wave. It is possible to predict the reflection peak due to offset of light and constructive interference. Furthermore, several reflected peaks may be optically encoded to allow for relative intensity adjustment at desired wavelengths.

More specifically, the multi-layer porous silicon (PSi) of the present invention is a p-type silicon wafer having a resistance of 0.1 ~ 10 mΩ㎝ through electrochemical etching using a mixture of hydrofluoric acid (HF) and ethanol, micropores ) Is mesopore (mesopore) pores of the size of 2 to 50nm, the pore size is prepared with a structure having micropores (micropores) of less than 2nm or macropores (pores) exceeding 50nm. At this time, the pore shape, size and direction of the porous silicon is determined according to the surface resistance and the degree of impurities of the crystalline silicon, the flowing current, the temperature, and the concentration of the hydrofluoric acid (HF) solution used during etching. Specifically, increasing the amount of impurities and diluting the concentration of hydrofluoric acid (HF) solution increases the pore size of the p-type porous silicon. In other words, when electrochemical etching is performed in a 25% alcohol-containing hydrofluoric acid (HF) solution of p-type porous silicon having a large amount of impurities and a resistance value of 10 ^-3 mΩ㎝, macropores having a size of 25 to 100 nm are formed. Porous silicon is produced.

As shown in FIG . 1 , the multilayer porous silicon of the present invention has a full-width at half-maximum (FWHM) of 12 nm on average and at specific wavelengths of 575, 613, 658, 714, 781 nm. By showing the reflection spectrum, it has a very narrow and strong reflection spectrum. These reflection spectra can vary from visible to near ultraviolet region, depending on the current flowing through the etching.

Thereafter, the porous silicon obtained through the electrochemical etching process has a surface of Si-H. Accordingly, as the surface of the unstable porous silicon in the air or in the aqueous solution is transformed into oxidized porous silicon (PSi) having a Si—OH functional group by thermal oxidation, the image diagnostic drug carrier of the present invention is capable of thermal oxidation. It can be converted into optically encoded porous silicon dioxide (PSD) prepared through a biocompatible material, and at the same time facilitate the induction of the drug.

Then, the present invention is fixed to the target drug on the oxidized porous silicon dioxide (PSD) film surface, and then pulverized, prepared by the surface-induced porous silicon dioxide particles with a drug, and used as a drug carrier.

In the imaging diagnostic drug carrier of the present invention, the electrochemically etched porous silicon can increase the selectivity to micromolecules by using pulverized PSD particles to maintain optical properties and not damage pores.

The target drug to be applied to the imaging diagnostic drug carrier of the present invention can be applied without particular limitation as long as it is a drug capable of binding to the oxidized surface. In the present invention, camptothecin (CPT) is used.

Figure 2 shows the drug delivery system of the surface-induced PSD particles with the drug of the present invention, the drug derivative of the present invention is released by hydrolyzing the target drug fixed according to the pH of the buffer solution.

In particular, as shown in Figure 6 , in accordance with the pH of the buffer solution in the PSD particles surface-induced with the drug of the present invention, from the result of measuring the release rate of the drug, it is hydrolyzed under the pH 4 to 9 conditions of the buffer solution By measuring the release rate of the drug, the release rate of the drug can be monitored in real time and the amount of release of the drug can be predicted.

In addition, the PSD particle surface-induced by the drug of the present invention is controlled to release rate due to the hydrolysis of the drug in accordance with the pH of the buffer solution, it is possible to monitor in real time the degree of drug release from the porous silicon particles through the signal amplification process 8A , 8B, and 9 , and the amount of drug released can be predicted, which is useful as a drug carrier in a drug delivery system.

Further,

1) preparing a multilayer porous silicon by etching the silicon wafer by electrochemical method,

2) separating the multilayer porous silicon into the porous silicon film from the silicon wafer,

3) forming a porous silicon dioxide (PSD) film whose surface is oxidized by heating the porous silicon film at a temperature of 300 to 1200 ° C. for 1 to 3 hours; and

4) It provides a method for producing an image diagnostic drug carrier for producing PSD particles by inducing a target drug on the surface of the oxidized porous silicon dioxide (PSD) film, followed by grinding.

Figure 3 shows the manufacturing process of the surface-induced PSD particles with the drug of the present invention, hereinafter will be described step by step the manufacturing method of the image diagnostic drug carrier of the present invention.

In the manufacturing method of the present invention, the porous silicon of step 1) is a multi-layer porous silicon electrochemically etched using a sine wave current, and has a single reflection peak at 400 to 2000 nm or 2 at 400 to 2000 nm. Multi-layer porous silicon having from 30 to multiple reflection peaks.

In more detail, as a preferred embodiment of the multilayer porous silicon, the center current value is 120 to 200 mA / cm 2, and is electrically etched using 2 to 30 sinusoidal mixed currents, and then, 2 to 400 to 2000 nm. It is to use from 30 to multiple multiple peaks (Rugate Multiple Peak).

Further, in another embodiment an example preferred for the multi-layer porous silicon is one or a rectangular-wave to a 50 mA / cm ² current to 1-200 seconds, 10 ~ 500 mA / cm ² current for shift from one to 30 seconds of the condition In the present invention, the present center current and the current higher than the center current are performed twice or more, and those having 2 to 30 multiple reflection peaks (DBR multiple peaks) at 400 to 2000 nm are used.

More preferably, in the embodiment of the present invention, the multi-layered porous silicon having a rugate structure has a half band width value of 12 nm on average and shows reflection spectra at specific wavelengths of 575, 613, 658, 714, and 781 nm [Fig. 1]. .

In the manufacturing method of the present invention, step 2) is a step of separating the multilayer porous silicon prepared in step 1) on the silicon wafer to produce a porous silicon film, the separation method of tweezers the porous silicon wafer, so as not to damage the film Grab it and let ethanol flow out of the glass plate to separate the porous silicon from the silicon wafer.

Then, in the manufacturing method of the present invention, step 3) is because the surface (Si-H) of the porous silicon obtained in the electrochemical etching process is unstable in the air or aqueous solution, thermal oxidation of the surface of the porous silicon, the surface is Si A process of transforming into oxidized porous silicon dioxide (PSD) having —OH functionality.

From the FT-IR spectra of FIG. 4 , the thermal oxidation process of step 3) reduces the stretching vibration and bending vibration region of Si-H, and confirms the vibration absorption peak of Si-O-Si, thereby oxidizing the surface. You can check it.

The optically encoded PSD prepared through the process of step 3) can be converted into a biocompatible material and at the same time facilitate the induction of the target drug on its surface.

At this time, the thermal oxidation method of step 3) is preferably carried out in a furnace (furnace), and if the heating temperature is less than 300 ℃, the oxidation reaction proceeds slowly and is not preferable, if it exceeds 1200 ℃, oxidized porous silicon This unstable and broken problem occurs.

In the manufacturing method of the present invention, step 4) is a process of producing PSD particles by induction of a target drug on the surface of the oxidized PSD film and then grinding.

In the present invention, as a target drug, camptothecin (CPT), which is used as an anticancer agent, is described as an example, but if it can bind to an oxidized surface (Si-OH), other known drugs can be applied as target drugs. Of course it will be understood.

As shown in Figures 2 and 3, the Si-OH of the oxidized PSD film and the OH of the camptothecin (CPT) of the target drug of the present invention is dehydrated, the Si-O-C bond is formed. Afterwards, the PSD particles bound to the CPT are ground to a nanoscale particle size at several microns.

At this time, in order to maintain the optical properties of the pulverized particles should not be damaged to the generated pores, a method by physical impact is also possible, but more preferably by a pulverization method using ultrasonic waves.

In addition, the PSD film combined with the CPT of the present invention has an advantage of easily obtaining particles through ultrasonic grinding because it is very thin (~ several microns). 7a and 7b] can be prepared without damaging the resulting pores. The weak nanonetwork structure thus obtained can be easily broken and obtained as individual particles of various sizes.

Thus, in step 4) of the manufacturing method of the present invention, by using the pulverized particles in the form of pulverized particles so as to maintain the optical properties and not damage the pores by the ultrasonic pulverization method, it is possible to increase the selectivity to the fine molecules have.

Hereinafter, the present invention will be described in more detail with reference to Examples.

This embodiment is intended to illustrate the present invention in more detail, and the scope of the present invention is not limited to these examples.

<Example 1> Preparation of the image diagnostic drug carrier using the lugate porous silicon smart particles

Step 1: Preparation of Optically Encoded Multilayer Porous Silicon

Pure p ⁺⁺ - type silicon wafer (B dopped, <100>, 0.8 ~ 1.2 mΩ㎝) using a platinum electrode and a constant current group (Galvanostat, Keithley 2420) the strength of the current 5.3 ~ 120.8 mA and through cm ^{- 2} in the 0.30, 0.33, 0.36, 0.39, the five kinds of mixed sine wave of 0.42Hz main surface flow during 2000 seconds after the electrochemical etching process, the optical encoding having a porosity (pore) and depth (depth) of a pattern base The multilayer porous silicon of the gate structure was prepared.

In this case, as an etching solvent for synthesizing porous silicon having a predetermined pattern of pores and depths, hydrofluoric acid (HF, 48% by weight, Aldrich Chemical Co., Ltd.) and ethanol (Aldrich Chemical Co., Ltd.) are 3: 1. The mixture was used in volume ratio, and all the processes were performed in a Teflon cell. After etching, the resultant was washed with ethanol and argon gas and dried.

Step 2: Separation of Porous Silicon Film

The multilayer porous silicon prepared in step 1 was separated from the silicon substrate into a film through electropolishing. At this time, electropolishing was also performed in the Teflon cell as in the preparation of multilayer porous silicon.

Using a potentiostat / Galvanostat 363 model (EG & E Instrument), a constant current of 460 mA cm ⁻² was flowed for 1 minute 30 seconds. At this time, the solvent used was a solvent prepared in a volume ratio of HF: ethanol = 3: 1. Thereafter, a constant current of 29 mA · cm ⁻² was flowed for 1 minute and 30 seconds using a solvent prepared at a volume ratio of HF: ethanol = 3: 1. The porous silicon substrate was held with tweezers to separate the multilayer porous silicon film from the silicon substrate by flowing ethanol so as not to damage the film on the glass plate.

Step 3: Preparation of Thermal Oxidation-Porous Silicon Dioxide (PSD)

The multilayer porous silicon film separated in step 2 was subjected to thermal oxidation for 6 hours at 300 ° C. in an electric furnace (Thermolyne F6270-26 furnace equipped with controller). Through the thermal oxidation, the multilayer porous silicon film terminated with Si-H was transformed into porous silicon dioxide (PSD) having Si-OH functionality.

Step 4: Derivatization of PSD Film and Preparation of PSD Particles

The porous silicon dioxide (PSD) film prepared in the above step was 13.8 mg of CPT (0.05 mmol, ˜95%, Aldrich Chemical Co., Ltd.) and 13 mg of dimethylaminopyridine (0.1 mmol Aldrich Chemical Co., Ltd.) as a catalyst. It was dissolved in 10 ml of dichloromethane and stirred at room temperature for 3 days. After the reaction was completed, the mixture was washed with ethanol, dichloromethane, acetone, and then dried with argon gas.

Subsequently, when the surface-induced porous silicon dioxide (PSD) film was pulverized by using an ultrasonic grinder for about 5 to 10 minutes, the porous silicon dioxide (PSD) particles induced by the drug having optical properties were prepared.

Example 2 Fabrication of Image Diagnosis Drug Carrier Using DBR Porous Silicon Smart Particles

Step 1: Preparation of DBR Multilayer Porous Silicon

A p ⁺⁺ -type silicon single crystal wafer (B dopped, <100>, 0.8∼1.2 mΩ · cm) having a low resistance value was electrochemically etched using a current supply (Keithley 2420) by flowing a rectangular wave current. DBR multilayer porous silicon was prepared. HF solution (48 wt% Aldrich) and pure ethanol (Aldrich) were used as an etching solvent and etched at a volume ratio of HF: ethanol = 3: 1. Electrochemical etching was performed in Teflon cells using two electrodes. At this time, the flowed current alternately flows 30 mA / cm 2 corresponding to a low current for 11 seconds and 300 mA / cm 2 corresponding to a high current for 1.5 seconds to generate different porosity periodically changed. Was performed twice. DBR porous silicon samples synthesized under the above conditions were washed several times with ethanol after etching and dried with argon gas before use.

Hereinafter, steps 2 to 4 were carried out in the same manner as in Example 1 to produce an image diagnosis drug carrier.

Experimental Example 1 FT-IR Spectrum Measurement

The reaction of each step of preparing optically encoded multilayer porous silicon and porous silicon dioxide (PSD) particles in Example 1 was confirmed using FT-IR (Nicolet model 5700). The FT-IR spectra were measured using a Spectra-Tech diffuse reflectance attachment method.

As a result, as shown in Figure 4 , the FT-IR spectrum of the etched porous silicon (A) confirmed the stretching and bending vibration of Si-H at 2119cm ^-1 and 914cm ^-1 , and thermally oxidized porous silicon In the case of the film (B), the peak of 2085-2150 cm ^-1 , which is the stretching vibration region of Si-H, is reduced, and the stretching and bending vibration of OSi-H appear in 2200-2250cm ^-1 and 877cm ^-1 , respectively, and 1000- The strong vibration absorption peak of Si-O-Si was confirmed at 1200cm ^-1 . Accordingly, the etched porous silicon (A) was heated in a furnace at 300 ° C. for 6 hours to confirm oxidation of the surface of the porous silicon film.

In addition, the FT-IR spectrum shown in Figure 5 , the surface-induced porous silicon dioxide (PSD) film (C) of CPT confirmed the absorption peak at 3300cm ^-1 corresponding to the stretching vibration of the Si-OC bond, By confirming the peak at 1650 cm ^-1 corresponding to the bending vibration of the Si-OC bond, the surface of the PSD film having Si-OH was reacted with CPT to confirm that the surface was induced with CPT.

Subsequently, in the porous silicon dioxide (PSD) film (C) surface-induced by CPT, after the CPT hydrolysis reaction, in the case of the PSD film (D) in which the CPT is released, it can be seen that the absorbance is reduced in the CPT region.

Experimental Example 2 Measurement of CPT Release

In order to determine the amount of emission of CPT from the surface-induced porous silicon dioxide (PSD) particles in Example 1, it was measured using an ultraviolet spectrophotometer (UV-vis spectrometer, UV-2401 PC, Shimazu). At this time, it was fixed at 368nm, the maximum absorption wavelength of CPT, and the change in real time absorbance was measured for 12 hours.

As shown in FIG. 6, CPT combined with PSD particles is hydrolyzed and released according to the pH of the buffer solution, which is the fastest at pH 9 and the slowest release at pH 4.

As a result, the surface-induced porous silicon dioxide (PSD) particles of the present invention can control the release rate of the drug, depending on the pH.

Experimental Example 3 Measurement of Light Reflection Spectrum

1. Reflection Spectrum of Thermally Oxidized PSD Particles

With respect to the optically encoded multilayer porous silicon prepared in Example 1 and porous silicon dioxide (PSD) particles prepared by thermal oxidation, LS-1 (tungsten-halogen lamp) and an optical microscope equipped with an optical microscope (Ocean Optics) The optical reflectance spectra were measured using a charge coupled device (USB-2000). At this time, all the spectra were obtained by projecting the incident light vertically so that the projected light and the reflected light were on the same axis. The light source focused on the surface of the porous silicon at a point of about 1 to 2 mm, and the spectra recorded a 400 to 1200 nm wavelength region through a CCD detector.

FIG. 7A shows optically encoded multilayer porous silicon, and FIG. 7B shows real-time optical signal change of PSD particles prepared by thermal oxidation, wherein the PSD particles have only changed chemical properties by thermal oxidation. This optical property was confirmed to be maintained as it is.

2. Reflection spectrum of PSD particles during drug release

As the CPT bound to the surface of PSD particles is broken, the reflection peak is displaced by a short wavelength due to the change in refractive index that occurs, and the displacement width of the point where the CPT starts to be emitted or the emitted point is insignificant. By transforming the difference in displacement shifted to shorter wavelengths in a way that amplifies the change, a slight change can also amplify the signal.

In the case of CPT emission, the reflection spectrum measured from the PSD particles in real time is represented by a signal amplification method using a differential signal.

Therefore, FIG. 8A shows the reflection spectrum of the point at which the drug starts to be released (for 0 minutes and 10 minutes) as a differential signal, and it is not easy to identify the displacement of the drug when the drug is released . Minutes and 720 minutes) of the reflection spectrum as a differential signal, the amplification of the signal through the differential signal it was easy to identify the displacement point from which the CPT is released from the PSD particles.

In addition, the point at which the absorbance of the CPT emitted from the ultraviolet spectrophotometer can be identified is approximately 0.1 abs, which is 1.2 × 10 ⁻⁵ M when calculated in molarity.

However, in the differential signal represented by signal amplification, the molar concentration at the point 10 minutes after CPT is released by hydrolysis reaction is 4.9 × 10 ^-9 M. This proves that the detection of CPT emission is about 100 times better in PSD particles that can detect optical signals than ultraviolet spectrophotometers.

As a result, PSD particles can monitor the relationship between the degree of release of CPT and optical information, making it possible to directly read the information and use it as a new biocompatible drug delivery material.

9 is a result of measuring the intensity of the signal for each time zone, it was confirmed that the trend similar to the result of measuring the release rate of the drug according to the pH in the surface-induced porous silicon dioxide (PSD) particles with the drug shown in FIG. In other words, by confirming the increase of the absorption peak of the CPT released from the PSD particles, the PSD particles can be used as a drug carrier material that can directly read the information by monitoring the relationship between the release of the drug and the optical information Can be.

As described above, the present invention

First, an image diagnosis drug carrier using a biocompatible silicone material was provided.

Second, by preparing a multi-layer porous silicon film by an electrochemical etching method, and thermally oxidized the surface to secure a biocompatible porous silicon material, by fixing the drug on the oxidized porous silicon surface, by providing a pulverized porous silicon particles In addition, it can be applied as a novel imaging diagnostic drug delivery system in drug delivery system.

Third, the imaging diagnostic drug carrier of the present invention is controlled by the release rate due to hydrolysis of the drug in accordance with the pH of the buffer solution, it is possible to monitor the degree of drug release from the porous silicon particles in real time through the signal amplification process, The amount of drug released can be predicted.

Although the present invention has been described in detail only with respect to the described embodiments, it will be apparent to those skilled in the art that various modifications and variations are possible within the technical scope of the present invention, and such modifications and modifications belong to the appended claims. .

1 is a light reflection spectrum of multilayer porous silicon (PSi) of the present invention,

Figure 2 illustrates a drug delivery system of porous silicon dioxide (PSD) particles surface-induced with the drug of the present invention,

Figure 3 shows the manufacturing process of the surface-induced PSD particles with the drug of the present invention,

4 is an FT-IR spectrum result of the etched porous silicon (A) and the thermally oxidized porous silicon film (B) of the present invention,

5 is FT-IR spectra results of the PSD film (C) surface-induced with the CPT of the present invention and the PSD film (D) released CPT,

6 is a result of measuring the release rate of the drug according to the pH of the complete solution in the surface-induced PSD particles with the drug of the present invention,

FIG. 7A is a result of the change in the reflection spectrum of measuring the real-time optical signal change of the drug release point (for 0 minutes and 10 minutes) for the thermally oxidized PSD particles of the present invention.

FIG. 7B is a result of the change in the reflection spectrum of measuring the real-time optical signal change of the drug release point (for 0 and 720 minutes) for the thermally oxidized PSD particles of the present invention.

FIG. 8A illustrates the reflection spectrum at the time of drug release (for 0 minutes and 10 minutes) of FIG. 7A as a differential signal in the imaging diagnostic drug carrier of the present invention.

FIG. 8B shows the reflection spectrum of the drug release time point (for 0 minutes and 720 minutes) of FIG. 7B as a differential signal,

9 is a result of measuring the intensity of the signal of the surface-induced PSD particles with the drug of the present invention over time.

Claims (8)

The porous silicon film having 2 to 30 multiple reflection peaks prepared by the electrochemical etching method is thermally oxidized, the target drug is fixed on the surface of the oxidized porous silicon dioxide (PSD) film, and then pulverized and surface-induced with the drug. Made of porous silicon dioxide particles, The porous silicon film is The center current value is 120 to 200 mA / cm 2, and is electrically etched using a mixed current of 2 to 30 sinusoidal waveforms, and 2 to 30 multiple reflection peaks at 400 to 2000 nm or The center current is 1 to 50 mA / cm 2, and the current is 1 to 200 seconds, and the current of 10 to 500 mA / cm 2 is a rectangular wave under alternating conditions. The drug delivery carrier, characterized in that the two times more than each, having 2 to 30 multiple reflection peaks (DBR Multiple Peak) at 400 ~ 2000nm. The drug delivery carrier according to claim 1, wherein the surface-induced porous silicon dioxide particles are hydrolyzed under pH 4-9 conditions of the buffer solution to control the release rate of the drug. The drug carrier according to claim 1, wherein the porous silicon dioxide (PSD) film is treated at a temperature of 300 to 1200 ° C. for 1 to 3 hours and the surface is thermally oxidized to -Si-OH. The drug delivery carrier according to claim 1, wherein the target drug is camptothecin. delete 1) preparing a porous silicon having 2 to 30 multiple reflection peaks by etching the silicon wafer by an electrochemical method, 2) separating the porous silicon into the porous silicon film from the silicon wafer, 3) forming a porous silicon dioxide (PSD) film whose surface is oxidized by heating the porous silicon film at a temperature of 300 to 1200 ° C. for 1 to 3 hours; and 4) including the step of pulverizing after inducing the target drug on the surface of the oxidized porous silicon dioxide (PSD) film, The porous silicon of step 1) is 120-200 mA / cm 2 of the center current, and is electrically etched using 2 to 30 sinusoidal mixed currents, and 2 to 30 multiple reflection peaks at 400 to 2000 nm ( Rugate Multiple Peak) method for producing a drug carrier, characterized in that. 1) preparing a porous silicon having 2 to 30 multiple reflection peaks by etching the silicon wafer by an electrochemical method, 2) separating the porous silicon into the porous silicon film from the silicon wafer, 3) forming a porous silicon dioxide (PSD) film whose surface is oxidized by heating the porous silicon film at a temperature of 300 to 1200 ° C. for 1 to 3 hours; and 4) including the step of pulverizing after inducing the target drug on the surface of the oxidized porous silicon dioxide (PSD) film, Under the condition of orthogonal wave in which the porous silicon of step 1) has a center current value of 1 to 50 mA / cm ² , alternating currents of 1 to 200 seconds and 10 to 500 mA / cm ² for 1 to 30 seconds, The method of manufacturing a drug carrier, characterized in that the center current and the current that is higher than the center current is twice or more, each having 2 to 30 multiple reflection peaks (DBR multiple peaks) at 400 to 2000 nm. 8. The method of claim 6, wherein the ground porous silicon dioxide (PSD) particles of step 4) are ultrasonically ground.

Images