Ciprofloxacin PLGA nanoparticle

Abstract

The invention discloses a ciprofloxacin PLGA (poly (lactic-co-glycolic acid)) nanoparticle, and particularly relates to a method for preparing the ciprofloxacin-entrapped PLGA nanoparticle by taking benzyl alcohol as a solvent to dissolve ciprofloxacin and then selecting a nanoprecipitation method. The process adopted by the invention is simple and convenient to operate, the solubility of ciprofloxacin in water is effectively improved, and the prepared ciprofloxacin PLGA nanoparticles are spherical, round in appearance, uniform in particle size, good in encapsulation efficiency and good in slow release effect.

Description

Technical Field

[0001] The invention belongs to the technical field of biomedicine, and in particular relates to ciprofloxacin PLGA nanoparticles. Background Art

[0002] Ciprofloxacin is a chemically synthesized fluoroquinolone drug with a broad-spectrum antibacterial effect. It mainly inhibits the replication of bacterial DNA by inhibiting the unwinding of bacterial DNA superhelical structure, and has a strong destructive effect on bacterial cell walls, thus showing a strong bactericidal effect. It is a recommended drug for the treatment of aerobic bacterial vaginitis. However, in actual medication, due to the patient's bad medication habits such as abuse of antibiotics, drug-resistant strains will be produced. At the same time, since most of the vaginal preparations currently on the market are rapid-release preparations, frequent administration is required, and patient compliance is low. These are the limitations of traditional vaginal preparations. Studies have shown that polymer nano-drug delivery systems can effectively combat bacterial resistance mechanisms and enhance the antibacterial effect of antibiotics. In addition, their sustained-release effect can effectively reduce the frequency of administration and improve patient compliance. Therefore, the development of nano-drug delivery systems for the treatment of vaginitis is of great significance.

[0003] Since ciprofloxacin is almost insoluble in water and cannot be dissolved in common organic solvents, it is difficult to prepare ciprofloxacin PLGA nanoparticles using conventional methods such as single emulsion method and nanoprecipitation method. At present, some scholars have prepared ciprofloxacin hydrochloride PLGA nanoparticles by double emulsion method, which enhances the antibacterial activity and sustained release effect of the preparation, but its encapsulation rate is less than 50% [International Journal of Pharmaceutical, 2008, 352 (1-2): 317-323.]; some scholars have also synthesized ciprofloxacin-SDS complex to improve its solubility in organic solvents, and then prepared PLGA nanoparticles by nanoprecipitation method, and the final preparation encapsulation rate is about 70%, and the antibacterial activity of the preparation is enhanced, but its preparation process is relatively complicated [International Journal of Pharmaceutical, 2016, 511 (2): 994-1001.]. Therefore, it is of great application value to develop a ciprofloxacin PLGA nanoparticle with simple preparation process, good encapsulation rate and sustained release effect. Summary of the invention

[0004] The object of the present invention is to provide a ciprofloxacin PLGA nanoparticle, which is prepared by the following steps:

[0005] Step 1, dissolving ciprofloxacin in benzyl alcohol and PLGA in acetone, and mixing the two to obtain a drug-containing organic phase;

[0006] Step 2, dissolving PVA in water to obtain an aqueous phase;

[0007] Step 3, adding the drug-containing organic phase dropwise to the aqueous phase under stirring, stirring to remove the organic solvent, and obtaining a nanoparticle solution.

[0008] Furthermore, in step 1, the mass ratio of ciprofloxacin to PLGA is 1:8 to 1:24, preferably 1:16 to 1:24, and optimally 1:20; the volume ratio of benzyl alcohol to acetone is 1:4 to 1:6, preferably 1:4.5 to 1:5.5, and optimally 1:5; and the concentration of PLGA in the drug-containing organic phase is 5.0 to 15 mg / mL, preferably 7.5 to 12.5 mg / mL, and optimally 10 mg / mL.

[0009] Furthermore, in step 1, the PLGA is carboxyl terminated, has a relative molecular weight of 12,000, and a molar ratio of lactic acid to glycolic acid monomers in the block is 50:50.

[0010] Furthermore, in step 2, the concentration of the PVA is 0.25-1.25% w / v, preferably 0.5-1%, and optimally 0.75%.

[0011] In an embodiment of the present invention, the PVA is PVA1788.

[0012] Furthermore, in step 3, the volume ratio of the drug-containing organic phase to the aqueous phase is 1:2 to 1:6, preferably 1:4; and the stirring speed is 400 to 1000 rpm, preferably 800 rpm.

[0013] The inventors learned from previous experiments that ciprofloxacin is soluble in benzyl alcohol, so the solvent was selected to dissolve ciprofloxacin. Then, the nanoprecipitation method was used to prepare PLGA nanoparticles loaded with ciprofloxacin. The nanoparticles prepared under the optimal conditions had a particle size of (240.24±0.65), a PDI of (0.090±0.008), a relatively uniform particle size distribution, a Zeta potential of (-2.30±0.19), and a final encapsulation rate of the nanoparticles of (74.76±2.73)%.

[0014] Compared with the prior art, the present invention has the following beneficial effects:

[0015] 1. The present invention provides a method for preparing ciprofloxacin PLGA nanoparticles, which has simple process, convenient operation and effectively improves the solubility of ciprofloxacin in water.

[0016] 2. The present invention adopts PLGA as a drug carrier, which has good biocompatibility, degradability, non-toxicity and non-irritation.

[0017] 3. The ciprofloxacin PLGA nanoparticles prepared by the present invention are spherical, round in appearance, uniform in particle size, good in encapsulation efficiency, and have good sustained-release effect. BRIEF DESCRIPTION OF THE DRAWINGS

[0018] Figure 1 The encapsulation efficiency results of nanoparticles at different drug loading ratios.

[0019] Figure 2 The encapsulation efficiency of nanoparticles under different ratios of benzyl alcohol to acetone.

[0020] Figure 3 The encapsulation efficiency of nanoparticles at different PLGA concentrations.

[0021] Figure 4 The encapsulation efficiency of nanoparticles at different PVA contents.

[0022] Figure 5 The encapsulation efficiency of nanoparticles under different oil-water ratios.

[0023] Figure 6 The encapsulation efficiency of nanoparticles at different stirring speeds.

[0024] Figure 7 Transmission electron microscopy image of PLGA nanoparticles loaded with ciprofloxacin.

[0025] Figure 8 The in vitro release curves of ciprofloxacin in free solution and PLGA nanoparticles. DETAILED DESCRIPTION

[0026] The preferred embodiments of the present invention will be described in detail below in conjunction with examples. It should be understood that the following examples are provided only for the purpose of illustration and are not intended to limit the scope of the present invention. Those skilled in the art may make various modifications and substitutions to the present invention without departing from the purpose and spirit of the present invention.

[0027] Unless otherwise specified, the experimental methods used in the following examples are conventional methods.

[0028] Unless otherwise specified, the materials and reagents used in the following examples can be obtained from commercial sources.

[0029] In the following examples, the PVA used is PVA1788.

[0030] Example 1

[0031] This embodiment adopts nanoprecipitation method to prepare PLGA nanoparticles loaded with ciprofloxacin, comprising the following steps:

[0032] Step 1, dissolving ciprofloxacin in benzyl alcohol and PLGA in acetone, and mixing the two to obtain a drug-containing organic phase;

[0033] Step 2, dissolving PVA in purified water to obtain an aqueous phase;

[0034] Step 3, adding the drug-containing organic phase dropwise to the aqueous phase under stirring conditions, removing the organic solvent under low-speed stirring to obtain a nanoparticle solution.

[0035] Prescription Investigation

[0036] (I) Investigating the effect of drug loading ratio on the preparation of PLGA nanoparticles loaded with ciprofloxacin

[0037] 1. The mass of fixed PLGA is 30 mg and dissolved in 2.5 mL of acetone. According to the drug loading ratio shown in Table 1, the corresponding mass of ciprofloxacin is accurately weighed and dissolved in 0.5 mL of benzyl alcohol. The two are mixed to obtain a drug-containing organic phase;

[0038] 2. Accurately weigh the prescribed amount of PVA and dissolve it in purified water to obtain a 0.5% PVA aqueous phase;

[0039] 3. Under magnetic stirring, use a syringe (No. 5 needle) to add the drug-containing organic phase drop by drop into 12 mL of the aqueous phase at a stirring speed of 800 rpm. Continue stirring to evaporate the organic solvent to obtain a nanoparticle solution.

[0040] The sample particle size, PDI and Zeta potential were measured by nanoparticle size and Zeta potential analyzer, and the measurement was repeated three times. The encapsulation efficiency of nanoparticles was determined by high-speed centrifugation: the nanoparticle solution was centrifuged at 20,000 rpm for 60 min, and the supernatant was taken to determine the free drug content W 游离 The nanoparticle solution was centrifuged at 3000 rpm for 5 min to remove the precipitated large drug particles, and the supernatant was taken to determine the total drug amount W in the nanoparticle solution. 纳米粒 The encapsulation efficiency (EE%) was calculated according to the following formula, where W 投药量 The initial dosage is:

[0041]

[0042] The results are shown in Table 1 and Figure 1 shown.

[0043] Table 1. Nanoparticle size and Zeta potential results at different drug loading ratios ( n=3)

[0044] Drug loading ratio Particle size / nm PDI Zeta potential / mV 1:8 175.51±1.06 0.141±0.035 -2.06±0.46 1:12 183.44±3.84 0.028±0.030 -0.71±0.27 1:16 194.99±3.12 0.066±0.034 -1.34±0.45 1:20 217.42±8.89 0.080±0.035 -1.09±0.12 1:24 232.59±3.07 0.063±0.050 -0.03±0.15

[0045] From the above results, it can be seen that as the dosage decreases, that is, the PLGA ratio increases relatively, the encapsulation rate gradually increases, and when the drug loading ratio is 1:20 to 1:24, the encapsulation rate is not much different. Therefore, the drug loading ratio in the present invention is preferably 1:20.

[0046] (II) Investigating the effect of the volume ratio of benzyl alcohol to acetone in the organic phase on the preparation of PLGA nanoparticles loaded with ciprofloxacin

[0047] 1. The drug-load ratio is fixed at 1:20, the total volume of the organic phase is 3 mL, and 30 mg of PLGA is accurately weighed and dissolved in the corresponding volume of acetone as shown in Table 2, and 1.5 mg of ciprofloxacin is accurately weighed and dissolved in the corresponding volume of benzyl alcohol, and the two are mixed to obtain a drug-containing organic phase;

[0048] 2. Accurately weigh the prescribed amount of PVA and dissolve it in purified water to obtain a 0.5% PVA aqueous phase;

[0049] 3. Under magnetic stirring, use a syringe (No. 5 needle) to add the drug-containing organic phase drop by drop into 12 mL of the aqueous phase at a stirring speed of 800 rpm. Continue stirring to evaporate the organic solvent to obtain a nanoparticle solution.

[0050] The sample particle size, PDI and Zeta potential were measured by nanoparticle size and Zeta potential analyzer, and the measurement was repeated three times. The encapsulation efficiency of nanoparticles was determined by high-speed centrifugation: the nanoparticle solution was centrifuged at 20,000 rpm for 60 min, and the supernatant was taken to determine the free drug content W 游离 The nanoparticle solution was centrifuged at 3000 rpm for 5 min to remove the precipitated large drug particles, and the supernatant was taken to determine the total drug amount W in the nanoparticle solution. 纳米粒 The encapsulation efficiency (EE%) was calculated according to the following formula, where W 投药量 is the initial dosage.

[0051]

[0052] The results are shown in Table 2 and Figure 2 shown.

[0053] Table 2. Nanoparticle size and Zeta potential results at different volume ratios of benzyl alcohol to acetone ( n=3)

[0054] <![CDATA[V 苯甲醇 :In 丙酮 ]]> Particle size / nm PDI Zeta potential / mV 1:4 245.33±9.47 0.074±0.078 -1.31±0.02 1:4.5 228.45±9.37 0.115±0.084 -1.03±0.31 1:5 217.42±8.89 0.080±0.035 -1.09±0.12 1:5.5 225.07±3.71 0.093±0.013 -1.04±0.31 1:6 218.64±2.71 0.066±0.022 -0.57±0.23

[0055] From the above results, it can be seen that when the ratio of benzyl alcohol to acetone is 1:5, the nanoparticle encapsulation efficiency is the largest and the particle size is appropriate. Therefore, the volume ratio of benzyl alcohol to acetone in the present invention is preferably 1:5.

[0056] (III) Investigating the effect of organic phase PLGA concentration on the preparation of ciprofloxacin-loaded PLGA nanoparticles

[0057] 1. The drug-carrier ratio was fixed at 1:20, the ratio of benzyl alcohol to acetone was 1:5, and the corresponding mass of PLGA was accurately weighed and dissolved in 2.5 mL of acetone according to the PLGA concentration shown in Table 3, and the corresponding mass of ciprofloxacin was accurately weighed and dissolved in 0.5 mL of benzyl alcohol, and the two were mixed to obtain a drug-containing organic phase;

[0058] 2. Accurately weigh the prescribed amount of PVA and dissolve it in purified water to obtain a 0.5% PVA aqueous phase;

[0059] 3. Under magnetic stirring, use a syringe (No. 5 needle) to add the drug-containing organic phase drop by drop into 12 mL of the aqueous phase at a stirring speed of 800 rpm. Continue stirring to evaporate the organic solvent to obtain a nanoparticle solution.

[0060] The sample particle size, PDI and Zeta potential were measured by nanoparticle size and Zeta potential analyzer, and the measurement was repeated three times. The encapsulation efficiency of nanoparticles was determined by ultracentrifugation: the nanoparticle solution was centrifuged at 20,000 rpm for 60 min, and the supernatant was taken to determine the free drug content W 游离 The nanoparticle solution was centrifuged at 3000 rpm for 5 min to remove the precipitated large drug particles, and the supernatant was taken to determine the total drug amount W in the nanoparticle solution. 纳米粒 The encapsulation efficiency (EE%) was calculated according to the following formula, where W 投药量 is the initial dosage.

[0061]

[0062] The results are shown in Table 3 and Figure 3 shown.

[0063] Table 3. Nanoparticle size and Zeta potential results at different PLGA concentrations ( n=3)

[0064] <![CDATA[C PLGA (mg / mL)]]> Particle size / nm PDI Zeta potential / mV 5.0 177.83±7.86 0.097±0.075 -2.96±0.18 7.5 194.99±3.12 0.066±0.034 -3.60±0.42 10.0 217.42±8.89 0.080±0.035 -1.09±0.12 12.5 230.16±5.91 0.084±0.032 -3.98±0.49 15.0 264.10±2.61 0.074±0.083 -2.83±0.15

[0065] From the above results, it can be seen that when the PLGA concentration is 10 mg / mL, the encapsulation efficiency of the nanoparticles is the highest and the particle size is appropriate. Therefore, the PLGA concentration in the organic phase of the present invention is preferably 10 mg / mL.

[0066] (IV) Investigating the effect of PVA content on the preparation of PLGA nanoparticles loaded with ciprofloxacin

[0067] 1. Accurately weigh 30 mg PLGA and dissolve it in 2.5 mL acetone. Accurately weigh 1.5 mg ciprofloxacin and dissolve it in 0.5 mL benzyl alcohol. Mix the two to obtain a drug-containing organic phase.

[0068] 2. Accurately weigh PVA according to Table 4 and dissolve it in purified water to obtain an aqueous phase with a specified content of PVA;

[0069] 3. Under magnetic stirring, use a syringe (No. 5 needle) to add the drug-containing organic phase drop by drop into 12 mL of the aqueous phase at a stirring speed of 800 rpm. Continue stirring to evaporate the organic solvent to obtain a nanoparticle solution.

[0070] The sample particle size, PDI and Zeta potential were measured by nanoparticle size and Zeta potential analyzer, and the measurement was repeated three times. The encapsulation efficiency of nanoparticles was determined by ultracentrifugation: the nanoparticle solution was centrifuged at 20,000 rpm for 60 min, and the supernatant was taken to determine the free drug content W 游离 The nanoparticle solution was centrifuged at 3000 rpm for 5 min to remove the precipitated large drug particles, and the supernatant was taken to determine the total drug amount W in the nanoparticle solution. 纳米粒。 The encapsulation efficiency (EE%) was calculated according to the following formula, where W 投药量 is the initial dosage.

[0071]

[0072] The results are shown in Table 4 and Figure 4 shown.

[0073] Table 4. Nanoparticle size and Zeta potential results at different PVA contents ( n=3)

[0074] PVA concentration (w / v,%) Particle size / nm PDI Zeta potential / mV 0.25 171.05±5.23 0.378±0.024 -4.80±0.48 0.50 217.42±8.89 0.080±0.035 -1.09±0.12 0.75 240.24±0.65 0.090±0.047 -2.30±0.19 1.00 273.30±4.59 0.056±0.013 -1.99±0.14 1.25 314.55±9.96 0.090±0.045 -1.95±0.34

[0075] From the above results, it can be seen that when the PVA concentration is 0.75%, the encapsulation rate is the largest and the particle size is appropriate. Therefore, the PVA content in the present invention is preferably 0.75%.

[0076] (V) Investigating the effect of oil-water ratio on the preparation of PLGA nanoparticles loaded with ciprofloxacin

[0077] 1. Accurately weigh 30 mg PLGA and dissolve it in 2.5 mL acetone. Accurately weigh 1.5 mg ciprofloxacin and dissolve it in 0.5 mL benzyl alcohol. Mix the two to obtain a drug-containing organic phase.

[0078] 2. Accurately weigh PVA and dissolve it in purified water to obtain an aqueous phase with 0.75% PVA;

[0079] 3. According to the oil-water volume ratio shown in Table 5, the drug-containing organic phase was added dropwise into the corresponding volume of the aqueous phase using a syringe (No. 5 needle) under magnetic stirring at a stirring speed of 800 rpm. The organic solvent was continuously stirred to volatilize to obtain a nanoparticle solution.

[0080] The sample particle size, PDI and Zeta potential were measured by nanoparticle size and Zeta potential analyzer, and the measurement was repeated three times. The encapsulation efficiency of nanoparticles was determined by ultracentrifugation: the nanoparticle solution was centrifuged at 20,000 rpm for 60 min, and the supernatant was taken to determine the free drug content W 游离 The nanoparticle solution was centrifuged at 3000 rpm for 5 min to remove the precipitated large drug particles, and the supernatant was taken to determine the total drug amount W in the nanoparticle solution. 纳米粒。 The encapsulation efficiency (EE%) was calculated according to the following formula, where W 投药量 is the initial dosage.

[0081]

[0082] The results are shown in Table 5 and Figure 5 shown.

[0083] Table 5. Nanoparticle size and Zeta potential results at different oil-water ratios ( n=3)

[0084] Oil-water ratio Particle size / nm PDI Zeta potential / mV 1:2 279.55±7.85 0.073±0.057 -1.09±0.38 1:3 265.26±11.72 0.087±0.052 -1.49±0.09 1:4 240.24±0.65 0.090±0.008 -2.30±0.19 1:5 229.33±11.57 0.036±0.057 -2.22±0.26 1:6 211.80±4.96 0.135±0.069 -1.71±0.33

[0085] From the above results, it can be seen that as the oil-water ratio increases, the particle size of the nanoparticles gradually decreases, and the Zeta potential remains basically unchanged. When the oil-water ratio is 1:4, the encapsulation rate is the largest and the particle size is appropriate. Therefore, the oil-water ratio in the present invention is preferably 1:4.

[0086] (VI) Investigating the effect of stirring speed on the preparation of PLGA nanoparticles loaded with ciprofloxacin

[0087] 1. Accurately weigh 30 mg PLGA and dissolve it in 2.5 mL acetone. Accurately weigh 1.5 mg ciprofloxacin and dissolve it in 0.5 mL benzyl alcohol. Mix the two to obtain a drug-containing organic phase.

[0088] 2. Accurately weigh PVA and dissolve it in purified water to obtain an aqueous phase with 0.75% PVA;

[0089] 3. Add the drug-containing organic phase drop by drop into 12 mL of the aqueous phase using a syringe (No. 5 needle) while stirring at the speed shown in Table 6. After the addition is complete, continue stirring to evaporate the organic solvent to obtain a nanoparticle solution.

[0090] The sample particle size, PDI and Zeta potential were measured by nanoparticle size and Zeta potential analyzer, and the measurement was repeated three times. The encapsulation efficiency of nanoparticles was determined by ultracentrifugation: the nanoparticle solution was centrifuged at 20,000 rpm for 60 min, and the supernatant was taken to determine the free drug content W 游离 The nanoparticle solution was centrifuged at 3000 rpm for 5 min to remove the precipitated large drug particles, and the supernatant was taken to determine the total drug amount W in the nanoparticle solution. 纳米粒。The encapsulation efficiency (EE%) was calculated according to the following formula, where W 投药量 is the initial dosage.

[0091]

[0092] The results are shown in Table 6 and Figure 6 shown.

[0093] Table 6. Nanoparticle size and Zeta potential results at different stirring speeds ( n=3)

[0094] Stirring speed / rpm Particle size / nm PDI Zeta potential / mV 400 345.07±3.27 0.110±0.071 -2.71±0.09 600 285.69±4.50 0.076±0.064 -1.36±0.14 800 240.24±0.65 0.090±0.008 -2.30±0.19 1000 237.38±10.00 0.091±0.014 -2.90±0.41 1200 238.33±11.61 0.046±0.068 -3.04±0.15

[0095] From the above results, it can be seen that when the rotation speed is 600-1000 rpm, the encapsulation rate remains basically unchanged, but at 600 rpm, the nanoparticles have a larger particle size and the liquid splashes at 1000 rpm. Therefore, the stirring speed in the present invention is preferably 800 rpm.

[0096] Example 2

[0097] The optimal formulation of Example 1 was used to prepare PLGA nanoparticles loaded with ciprofloxacin, and the specific steps were as follows:

[0098] Step 1, accurately weigh 30 mg of PLGA and dissolve it in 2.5 mL of acetone, accurately weigh 1.5 mg of ciprofloxacin and dissolve it in 0.5 mL of benzyl alcohol, and mix the two to obtain a drug-containing organic phase;

[0099] Step 2, accurately weigh PVA and dissolve it in purified water to obtain an aqueous phase with 0.75% PVA;

[0100] Step 3, adding the drug-containing organic phase dropwise into 12 mL of the aqueous phase using a syringe (No. 5 needle) while stirring at a rotation speed of 800 rpm. After the addition is completed, stirring is continued to evaporate the organic solvent to obtain a nanoparticle solution.

[0101] The prepared nanoparticles were evaluated for quality as follows:

[0102] (I) Particle size, PDI, Zeta potential and encapsulation efficiency

[0103] The final particle size of PLGA nanoparticles loaded with ciprofloxacin was (240.24±0.65), the PDI was (0.090±0.008), the particle size distribution was relatively uniform, the Zeta potential was (-2.30±0.19), and the encapsulation efficiency reached (74.76±2.73).

[0104] (II) Microscopic morphology observation

[0105] The morphology of the nanoparticles was observed using transmission electron microscopy. Figure 7 shown.

[0106] From the above results, it can be seen that the PLGA nanoparticles loaded with ciprofloxacin are round in appearance, present a smooth spherical shape, and have no aggregation phenomenon.

[0107] (III) In vitro release

[0108] The in vitro release of PLGA nanoparticles loaded with ciprofloxacin was studied by dynamic dialysis. The release medium was a PBS solution at pH 4.5, which was prepared as follows: 6.805 g of potassium dihydrogen phosphate was weighed, 1000 mL of purified water was added, and the mixture was stirred thoroughly until dissolved, and the pH value was adjusted to 4.5 with hydrochloric acid or sodium hydroxide solution. 6 mL of free ciprofloxacin or nanoparticle solution (actual drug content was about 0.75 mg) was placed in a dialysis bag (MWCO≈12 kDa), the two ends of the dialysis bag were sealed with dialysis bag clamps, and the bag was immersed in 120 mL of release medium. The bag was oscillated at 37°C and 100 rpm, and 3.5 mL of samples were taken at 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, and 24 h, respectively, and the release medium of the same volume and temperature was immediately added. The drug concentration in the sample was determined, and the cumulative release was calculated according to the following formula.

[0109]

[0110] Where C1, C2, ..., C n represents the sample concentration of the 1st, 2nd, ..., nth sampling; V0 represents the initial volume of the release medium; V represents the sampling volume; W represents the total drug amount.

[0111] The results are as follows Figure 8 As shown, from the above results, it can be seen that PLGA nanoparticles loaded with ciprofloxacin have a sustained release effect on the drug.

Claims

1. A ciprofloxacin PLGA nanoparticle, characterized in that: Prepared using the following steps: Step 1, dissolving ciprofloxacin in benzyl alcohol and PLGA in acetone, and mixing the two to obtain a drug-containing organic phase; Step 2, dissolving PVA in water to obtain an aqueous phase; Step 3, adding the drug-containing organic phase dropwise to the aqueous phase under stirring, stirring to remove the organic solvent, and obtaining a nanoparticle solution.

2. The ciprofloxacin PLGA nanoparticles according to claim 1, characterized in that In step 1, the mass ratio of ciprofloxacin to PLGA is 1:8-1:24, the volume ratio of benzyl alcohol to acetone is 1:4-1:6; and the concentration of PLGA in the drug-containing organic phase is 5.0-15 mg / mL.

3. The ciprofloxacin PLGA nanoparticles according to claim 2, characterized in that In step 1, the mass ratio of ciprofloxacin to PLGA is 1:16-1:24, the volume ratio of benzyl alcohol to acetone is 1:4.5-1:5.5; and the concentration of PLGA in the drug-containing organic phase is 7.5-12.5 mg / mL.

4. The ciprofloxacin PLGA nanoparticles according to claim 1, characterized in that: The PLGA is carboxyl-terminated, has a relative molecular weight of 12,000, and a molar ratio of lactic acid to glycolic acid in its block is 50:

50.

5. The ciprofloxacin PLGA nanoparticles according to claim 1, characterized in that In step 2, the concentration of PVA is 0.25-1.25% w / v.

6. The ciprofloxacin PLGA nanoparticles according to claim 5, characterized in that In step 2, the concentration of PVA is 0.5-1% w / v.

7. The ciprofloxacin PLGA nanoparticles according to claim 1, characterized in that: The PVA is PVA1788.

8. The ciprofloxacin PLGA nanoparticles according to claim 1, characterized in that: In step 3, the volume ratio of the drug-containing organic phase to the aqueous phase is 1:2-1:6; and the stirring speed is 400-1000 rpm.

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