KR101314579B1 - Paclitaxel- loaded polymeric nanoparticle and preparation thereof - Google Patents

Abstract

The present invention relates to a polymer nanoparticle in which paclitaxel is shipped, wherein the nanoparticle includes a paclitaxel and a water-soluble polymer that is coated while surrounding the paclitaxel surface, and the polymer is poly [2- (die Methylamino) ethyl methacrylate-co-methacrylic acid] (poly [2- (dimethylamino) ethyl methacrylate- c -methacrylic acid], PDM), wherein the paritaxel according to the present invention is shipped Polymer nanoparticles are hydrophilic separators that surround paclitaxel, which are water-soluble and biocompatible, and effectively release paclitaxel drugs to cancer cells that have multi-drug resistance (MDR). In addition, it has an anticancer effect that is thousands of times higher than that of the existing natural paclitaxel.

Description

Paclitaxel-loaded polymeric nanoparticles and preparation method thereof {Paclitaxel-loaded polymeric nanoparticle and preparation}

The present invention relates to a polymer nanoparticle in which paclitaxel is shipped, and more particularly, paclitaxel capable of effectively delivering and releasing paclitaxel to cancer cells having biocompatibility and water-soluble properties and having multi-drug resistance. The present invention relates to a shipped polymeric nanoparticle and a method of manufacturing the same.

Cancer is one of the major global diseases because the disease symptoms are complicated and diagnosed in more than 10 million cases all over the world, and anticancer drugs are currently used for the treatment of cancer. Always causes a lot of problems.

In particular, the occurrence of multi-drug resistance (MDR) is a major obstacle in the treatment of cancer by anticancer drugs. The most common mechanism associated with MDR is the drug's inability to bind to cancer cells by the ATP binding-ABC transport protein, and the outflow. One of the ABC transport proteins, P-glycoprotein (P-glycoprotein encoded by MDR-1), has been reported to cause multidrug resistance (MDR). P-glycoprotein is a protein that serves to transport substances that are structurally and functionally specific to cancer cells, and overexpression of P-glycoprotein to tumor cells reduces drug accumulation in cells and Therefore, the therapeutic effect of anticancer drugs is reduced.

Accordingly, in order to overcome drug resistance by P-glycoprotein inhibitors, anticancer agents encapsulated with polymer nanoparticles that can interact with anticancer agents and P-glycoprotein have been reported.

Recently, interest in nanoparticles has increased in cancer treatment. Nanoparticles are of increasing interest due to their ability to cross certain biological barriers, immunological or nonspecific interactions that give rise to cytotoxic effects, and the ability to functionally bind certain polymers such as polyethylene glycol to prevent interaction with plasma proteins. Is holding.

In particular, nanoparticles enhance the intracellular accumulation of anticancer agents and the delivery of drugs into cells, making it easier to overcome drug resistance. For example, doxorubicin or paclitaxel, an anti-tumor antibiotic, is 6-fold higher than the inhibitory effect of cell activity on doxorubicin or paclitaxel itself due to the overexpression of P-glycoprotein in the human body. IC ₅₀ values as low as 9 times. In addition, the polycapololactan / poloxamer 188 polymer nanoparticles loaded with paclitaxel exhibited IC ₅₀ values that are up to 10 times lower than taxol, an anticancer drug taken from the yew tree against drug-resistant cells.

Paclitaxel, one of the major anticancer drugs, is a leading agent of new antitumor drugs extracted from the Pacific cedar (Taxus brevifolia). have.

However, due to insolubility in water, allergic hypersensitivity due to the problem of adding an adjuvant such as Cremophor® EL (polyethoxylated castor oil derivative) to the formulation and the toxicity of ethanol in chemotherapy treatment, It has side effects such as hyperlipidemia and synthesis of abnormal protein patterns.

Therefore, in order to increase the anticancer effect of paclitaxel and overcome drug resistance, the development of a complex of water-soluble and biocompatible paclitaxel and polymer nanoparticles is urgently needed.

Accordingly, the problem to be solved by the present invention is to effectively deliver paclitaxel to cancer cells having multidrug resistance by loading the paclitaxel and the paclitaxel in an amphoteric polyelectrolyte having both acid and base activity. To provide a polymer nanoparticles shipped with paclitaxel that can have an increased anti-cancer effect.

In addition, the present invention provides a method for producing the polymer nanoparticles in which the paclitaxel is shipped by the paclitaxel and the polymer material.

In order to achieve the above object,

Paclitaxel-loaded polymeric nanoparticles, the nanoparticles comprising paclitaxel and a water-soluble polymer that is coated surrounding the paclitaxel surface, wherein the polymer is poly [2- (dimethylamino) ethylmeta Cryrate-co-methacrylic acid] (poly [2- (dimethylamino) ethyl methacrylate- c -methacrylic acid], PDM) provides patritaxel-loaded polymeric nanoparticles.

In addition, the nanoparticles are mixed with a poly [2- (dimethylamino) ethyl methacrylate-co-methacrylic acid] copolymer and the paclitaxel and milled to form a complex, and then the complex is dissolved in water. And it provides a polymer nanoparticles shipped with paclitaxel, characterized in that prepared by centrifugation.

According to one embodiment of the present invention, the poly [2- (dimethylamino) ethyl methacrylate-co-methacrylic acid] copolymer comprises a methacrylic acid (MACA) monomer and 2-dimethylaminoethyl The methacrylate (2- (dimethylamino) ethyl methacrylate, DMAEMA) monomer can be prepared by radical polymerization in a nitrogen atmosphere.

According to an embodiment of the present invention, the molar ratio of MAA in the poly [2- (dimethylamino) ethyl methacrylate-co-methacrylic acid] which is the amphoteric polymer electrolyte may be 5-30%.

According to one embodiment of the present invention, the size of the polymer nanoparticles to which paclitaxel is shipped may be 120-600 nm.

The present invention provides an anticancer agent composition containing the polymer nanoparticles, wherein the paclitaxel is shipped as an active ingredient.

The paclitaxel-loaded polymer nanoparticles according to the present invention are hydrophilic polymers that surround paclitaxel and are not only water-soluble and biocompatible, but also cancer having multi-drug resistance (MDR). It effectively releases and delivers paclitaxel drugs to cells, and has an anticancer effect that is thousands of times higher than that of conventional natural paclitaxel.

Figure 1 is a schematic diagram showing a solid-state reaction (Solid-state reaction) for preparing the polymer nanoparticles shipped with paclitaxel according to an embodiment of the present invention. A is the structural formula of paclitaxel, B is the structural formula of PDM which is a copolymer.
2A is a TEM image showing paclitaxel.
2B is a SEM image showing the shape of paclitaxel that is pretreated and shipped to PDM according to one embodiment of the present invention.
Figure 2c is a graph showing the size of the nanoparticles according to an embodiment of the present invention.
FIG. 3 is a graph showing the degree of drug release from nanoparticles loaded with paclitaxel in different pH environments at (1) pH 5.2 and (2) pH 7.4.
FIG. 4 shows PAX (Paclitaxel solution), PP (Paclitaxel loaded polymer nanoparticles), PAX + ZQS (Paclitaxel and zosquidar mixed solution), PDM + PAX (Paclitaxel and PDM mixed solution) It is a graph showing the IC activity value IC ₅₀ of each.
FIG. 5A is a fluorescence image showing the intracellular distribution of FITC conjugated to nanoparticles loaded with paclitaxel according to the present invention for MCF7 cells.
FIG. 5B shows (1) unlabeled cells, (2) FITC-PP at 4 ° C. or less, (3) FITC-PP at 37 ° C., 10% carbon dioxide conditions, and (4) FITC-PP for MCF7 cells. Is a graph showing the results of flow cytometric analysis at 37 ° C. and 10% of carbon dioxide at 37 ° C. and pretreatment with ATP consumed conditions.
5C is a fluorescence image showing the intracellular distribution of FITC conjugated with nanoparticles loaded with paclitaxel according to the present invention for MCF7 / ADR cells.
5D shows (1) unlabeled cells, (2) FITC-PP at 4 ° C. or less, (3) FITC-PP at 37 ° C., 10% carbon dioxide condition, and (4) FITC for MCF7 / ADR cells. Pre-treatment of -PP with ATP-depleted conditions and flow cytometric results at 37 ° C. and 10% carbon dioxide conditions, respectively.

Hereinafter, the present invention will be described in detail.

The paclitaxel-loaded polymer nanoparticles according to the present invention is characterized in that it includes a paclitaxel of [Formula 1] and a water-soluble polymer coated while surrounding the paclitaxel surface.

[Structural formula 1]

The polymer is an amphoteric polyampholyte capable of ionizing both cations and anions, and having both an acid or a base activity. The polymer is poly [2- (dimethylamino) ethyl methacrylate-co-methacrylic acid] ( PDM).

The PDM is represented by the following [Formula 2], characterized in that it comprises a weak base ((2- (dimethylamino) ethyl methacrylate, D) portion and a weak acid portion (methacrylic acid, M) as a repetitive structure.

[Structural formula 2]

The PDM is an acid labile and decomposable substance, which can be decomposed at the acidic pH of tissues in the body to release paclitaxel, that is, in the case of tumors, it is generally acidic and effectively causes paclitaxel tumors. Release and deliver to tissue.

In addition, the poly [2- (dimethylamino) ethyl methacrylate-co-methacrylic acid] copolymer is a methacrylic acid (MAA) monomer and 2-dimethylaminoethyl methacrylate (2- ( dimethylamino) ethyl methacrylate, DMAEMA) monomers are prepared by radical polymerization in a nitrogen atmosphere, and are prepared in the poly [2- (dimethylamino) ethyl methacrylate-co-methacrylic acid] as the amphoteric polymer electrolyte. The molar ratio of the MAA may be 5-30%.

The present invention is characterized in that the pharmaceutical composition for treating cancer containing the polymer nanoparticles shipped with paclitaxel as an active ingredient, the cancer is leukemia, brain tumor, kidney cancer, stomach cancer, skin cancer, bladder cancer, breast cancer, It may be any one selected from the group consisting of uterine cancer, lung cancer, colon cancer, prostate cancer, ovarian cancer, liver cancer, colon cancer, peritoneal cancer, peritoneal metastasis cancer and pancreatic cancer.

The 'pharmaceutical composition' may include a pharmaceutically acceptable carrier, diluent, excipient, or combination thereof as needed with the nanoparticle compound of the present invention. The term 'carrier' refers to a substance that facilitates the addition of the compound into cells or tissues, and the term 'diluent' not only stabilizes the biologically active form of the compound of interest, but also dissolves the compound. Means a substance diluted in water.

Pharmaceutically acceptable carriers are conventionally used in the formulation, such as lactose, dextrose, sucrose, sorbitol, mannitol, starch, acacia rubber, calcium phosphate, alginate, gelatin, calcium silicate, microcrystalline cellulose, poly Vinylpyrrolidone, cellulose, water, syrup, methyl cellulose, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil, and the like.

In addition, the pharmaceutical composition is preferably administered parenterally. For parenteral administration, intravenous injection, intramuscular injection, intra-articular injection, intra-synovial injection, intramural injection, intrahepatic injection, intralesional injection or It may be administered by intracranial infusion or the like.

The appropriate dosage of the pharmaceutical composition of the present invention may vary depending on factors such as the formulation method, administration method, age, body weight, sex, pathological condition, food, administration time, administration route, excretion rate, .

Other terms and abbreviations used herein may be interpreted as meanings commonly understood by those skilled in the art to which the present invention belongs unless otherwise defined.

Hereinafter, the present invention will be described in more detail with reference to preferred embodiments. However, these examples are intended to illustrate the present invention in more detail, it will be apparent to those skilled in the art that the scope of the present invention is not limited thereby.

<Examples>

Production example. Preparation of Polymer Nanoparticles Shipped with Paclitaxel

(1) Methacrylic acid (MAA) as a monomer according to the nanoparticles of the present invention was purchased from Jassen, 2-dimethylaminoethyl methacrylate (2- (dimethylamino) ethyl methacrylate, DMAEMA) was purchased from Aldrich and used in the manufacture.

In addition, paclitaxel, an anticancer agent, was purchased from Bolak (Lot No. 200805001, South Korea), and doxorubicin hydrochloride was purchased from AK Scientific, Inc. (USA).

MTT reagents (thiazoyl blue tetrazolium bromide, 97.5% TLC), Bisbenzimide H 33258, Fluorescein isothiocyanate (FITC), sodium azaid, rhodamine 123 and 2-deoxy-D-glucose used in the MTT assay for cytotoxicity investigation were respectively sigma-aldrich Acetonitrile (HPLC Gradient grade) and DMSO were purchased from LAB-SCAN and Roth, and DMEM (GlutaMAX) and penicillin-streptomycin for cell culture were purchased from Gibco, and used with fetal bovine serum. (FBS) was purchased from PAA Laboratories GmbH and used.

(2) Synthesis of Amphoteric Polyelectrolyte

The poly [2- (dimethylamino) ethyl methacrylate-co-methacrylic acid] copolymer was synthesized by subjecting methacrylic acid and 2-dimethylaminoethyl methacrylate to a radical polymerization reaction in a nitrogen atmosphere.

The mole fraction of PDM was analyzed by elemental analysis (thermo Quest Analyzer, EA-1110), light scattering equipment (SLS, DLS-8000, Otsuka Electronics Co., Ltd., cylindrical optical cell (diameter: 1.9 cm)) The mass was analyzed using, and the specific refractive index of the copolymer was analyzed by DRM-3000 (Otsuka Electronics Co., Ltd.). The pH value was measured using a pH meter (ThermoOrion, Model 550A), and the surface charge of the copolymer PDM was measured using ELS-Z (Otsuka Electronics Co., Ltd.).

(3) Synthesis of polymer nanoparticles loaded with paclitaxel

Paclitaxel and PDM were mixed in a stainless capsule with a mixing ball, mixed at 20 Hz for 20 minutes at room temperature, dissolved in water at a concentration of 1 mg / ml, and centrifuged for 10 minutes to remove uncomplexed paclitaxel. In addition, water was added, and further centrifugation was continued to collect the supernatant, and the polymer nanoparticles loaded with paclitaxel were collected. The supernatant was then freeze-dried.

The shape and surface charge characteristics of the particles were measured by SEM and ELS, respectively. Then, the freeze-dried powder was dissolved in water and sonicated for 1 minute to confirm the particle size. Particle size was confirmed using light scattering equipment (DLS), and the loading efficiency of paclitaxel was observed by UV-Vis spectroscopy.

After the paclitaxel, which is the stick shape of FIG. 2A, is reacted with PDM in a solid phase, it may be confirmed that its shape is changed to a nano-sized spherical shape as shown in FIG. 2B. As the shape of paclitaxel changes to a spherical form of nanoparticle size, it affects drug release and drug dispersion mechanisms. In particular, nanoparticles smaller than 250 nm efficiently accumulate in tumor cells and exhibit anticancer effects.

In the case of the polymer nanoparticles shipped with paclitaxel prepared according to an embodiment of the present invention, the size of the dynamic light scattering (DLS) measurement result, as shown in FIG. 2C, confirms that the average particle size is 250 nm. It was.

Experimental Example

(1) drug release experiment

10 mg of paclitaxel loaded polymer nanoparticles were placed in the dialysis bag, and an acetate solution containing 2% fetal bovine serum and 0.02% sodium azide (pH 5.2) and phosphate buffer were tested for drug release. The solution (pH 7.4) was used as a releasing media.

Nanoparticles contained in the dialysis bag were placed in 20 ml of the releasing media and incubated at 37 ° C. The amount of paclitaxel was analyzed by high performance liquid chromatography (Zorbax C18 column (5 μm, 4.5 × 250 mm), water: acetonitrile = 45: 55, UV 230 nm).

(2) Cell culture

10% fetal bovine serum (FBS) and 1% penicillin streptomycin were incubated at 37 ° C with 10% carbon dioxide. Doxorubicin resistant cells, MCF7 / ADR and MT3 / ADR, were cultured in a medium containing 0.1 μg / ml doxorubicin.

(3) Evaluation of cytotoxicity

To confirm the anticancer effects on MCF7, MCF7 / ADR, MT3, and MT3 / ADR, colorimetric assay (MTT colorimetric assay) was used. MCF7 and MCF7 / ADR were seeded at a concentration of 1.5 × 10 ⁴ cells / well in 96 wells, and MT3 and MT3 / ADR were seeded at a concentration of 1.5 × 10 ⁴ cells / well, followed by 24 at 37 ° C. in a 10% carbon dioxide incubator. Incubated for hours.

(4) Cellular uptake analysis

For cell influx analysis, polymer nanoparticles loaded with fluorecein isothiocyanate (FITC) -paclitaxel were measured by flow cytometric analysis (FACS).

In polymer nanoparticles (FITC-PP) loaded with FITC-labeled paclitaxel, the isothiocyanate groups of FITC interact with the amine groups of PDM. FITC-PP was prepared by preparing a FITC solution dissolved in 1 mg / ml DMSO and incubating for 2 hours by adding 10 μl of FITC solution to 10 ml nanoparticle dispersion. FITC-PP was dialyzed for 2 days in the absence of light by cellulose dialysis membrane and water was changed every 12 hours.

For FACS analysis, MCF7 and MCF7 / ADR cells were incubated for 30 minutes at 37 ° C. and 4 ° C., or pretreated for 30 minutes using 10 mM NaN ₃ and 50 mM 2-deoxy-D-glucose. 0.1 μM FITC-PP was then treated with each pretreated cell.

(5) loading efficiency of paclitaxel

The efficiency was measured by ultraviolet and visible dry spectroscopy (UV-Vis spectroscopy), and the loading efficiency of paclitaxel can be measured by the correlation between the extinction coefficients of paclitaxel and PDM. Paclitaxel and PDM were measured at 280 nm and 230 nm, respectively. Measured at 280 nm and 230 nm, e _{PAX , 280} = 1225 L / molcm, e _{PAX , 230} = 28316 L / molcm, e _{PDM, 280} = 58529 L / molcm, e _{PDM , 230} = 649850 L / molcm. Thereby, the loading efficiency of paclitaxel according to the present invention was 57.62%.

(6) release of paclitaxel

The polymer nanoparticles to which paclitaxel is shipped have water solubility, characterized in that paclitaxel is surrounded by PDM, which is a water-soluble substance. Thus, control of the release of paclitaxel from the nanoparticles is determined according to the pH upon which PDM depends.

The PDM has an acid-labile and chemically decomposed functional group on the backbone or branch, so that the surface of the nanoparticles that shipped paclitaxel is decomposed to release the paclitaxel drug in response to pH. . As such, the drug can be effectively released by the system capable of delivering the drug in the cell in response to pH to deliver the drug to a specific tissue.

Typical tissue and blood have a pH of 7.4. However, most tumor tissues have a pH of 5.7-7.8. Therefore, the nanoparticles shipped with the paclitaxel drug according to the present invention can release and deliver the drug directly to cancer cells in response to pH, thereby having an excellent anticancer effect.

3 shows the degree of drug release from nanoparticles loaded with paclitaxel in different pH environments at (1) pH 5.2 and (2) pH 7.4, wherein the rate of paclitaxel release at pH 5.2 is shown in FIG. It can be seen that the pH is faster than 7.4, and after 24 hours of incubation, 30% increase in the acidic environment than pH 7.4, that is, about 60% is released.

(7) Inhibitory Effects of Paclitaxel Shipped Nanoparticles on Cancer Cells

Western blot and rhodamine 123 assay were used to confirm the resistance function due to overexpression of P-glycoprotein (P-gp) against MCF7, MCF7 / ADR, MT3 and MT3 / ADR.

In Table 4 and [Table 1] for cell activity effect IC ₅₀ for the nanoparticles according to the present invention The values are shown in comparison.

Cell line IC ₅₀ (nM) PAX PP PAX + ZQS PDM + PAX MCF7 0.93 ± 0.12 0.001 < 0.35 ± 0.01 10.43 ± 1.80 MCF7 / ADR > 20000 4.75 ± 0.54 26.94 ± 2.63 13650 ± 2570 MT3 5.28 ± 0.54 0.59 ± 0.15 0.27 ± 0.02 0.65 ± 0.49 MT3 / ADR 300.77 ± 31.05 2.92 ± 0.09 6.38 ± 0.48 > 20000

PAX: Paclitaxel Solution

PP: Polymer Nanoparticles with Paclitaxel Shipped

PAX + ZQS: Mixed solution of paclitaxel and zosquidar

PDM + PAX: Paclitaxel and PDM Mixed Solution

Referring to [Table 1], it can be seen that the polymer nanoparticles (PP) loaded with paclitaxel according to the present invention have a cancer cell inhibitory effect of several tens to several thousand times as compared to the natural paclitaxel (PAX). Compared with the mixed solution of paclitaxel and zosquidar added with zosquidar, which is known as an inhibitor of P-gp, it has similar effects on MT3 and effects on MCF7 / ADR. 6-8 times better effect.

(8) Evaluation of intracellular accumulation and intracellular internalization of nanoparticles

In order to confirm the intracellular accumulation and intracellular internalization of the paclitaxel-loaded polymer nanoparticles, fluorescence in isothiocyanate (FTIC) -PP (Paclitaxel) was analyzed using flow cytometric analysis (FACS) and confocal microscopy. Intracellular distribution of the nanoparticles shipped) was confirmed. Nuclei were labeled with bisbenzimide.

Drug-loaded nanoparticles are incorporated by cell membranes by endocytosis and increase their accumulation in cells, thereby increasing the therapeutic effect. In particular, for cancer cells having multi-drug resistance, the drug loaded on the nanoparticles in the polymer is amplified in the cell rather than being transported out of the cell by P-gp, thereby amplifying a therapeutic effect.

Endocytosis is inhibited at low temperatures (4 ° C.) or in environments with reduced ATP. In order to confirm this, 4 ℃, 37 ℃ ATP reduced environment (when pre-treatment with NaN ₃ and 2-deoxy-D-glucose), 37 ℃ in the general environment were respectively tested and the results are shown in Figures 5a to 5d Shown in

As shown in Figure 5a to 5d, it can be confirmed that the intracellular influx of the nanoparticles shipped with paclitaxel for MCF7, MCF7 / ADR. As a result, it can be seen from the fluorescence image that FITC-PP accumulates in the cells by endocytosis and is internalized in the cells, and thus, paclitaxel is effectively delivered to the cancer cells, thereby increasing the concentration in the cells. Paclitaxel according to the present invention will confirm the therapeutic effect by the shipped nanoparticles.

As such, the overexpression of P-gp encoded by the multidrug resistance gene brings about drug resistance in various chemical treatments for cancer and is a major obstacle in treating cancer cells.

Prytaxel-containing polymer nanoparticles prepared according to the present invention are surrounded by paclitaxel by a polymer having a hydrophilic surface, and the size of the nanoparticles is characterized in that the effective treatment of paclitaxel against specific cancer cells. It can be delivered and released quickly, resulting in an excellent anticancer effect against cells having drug resistance. In particular, it has an effect 100-4000 times better than natural paclitaxel.

As described above, the specific part of the present invention, its features, and effects have been described in detail, and for those skilled in the art, these specific technologies are merely preferred embodiments, and the scope of the present invention is limited thereto. It is obvious. Therefore, the substantial scope of the present invention will be defined by the appended claims and equivalents thereof.

Claims (7)

As a polymer nanoparticle shipped with paclitaxel,
The nanoparticles are paclitaxel; And a water-soluble polymer that is coated while surrounding the paclitaxel surface.
The polymer is a poly [2- (dimethylamino) ethyl methacrylate-co-methacrylic acid] copolymer comprising a (dimethylamino) ethyl methacrylate monomer and a methacrylic acid monomer, and methacryl in the polymer The molar ratio of acid is 5-30%,
The paclitaxel-loaded polymer nanoparticles were placed in a dialysis bag containing an acetate solution of pH 5.2 containing 2% fetal bovine serum (FBS) and 0.02% sodium azide, and incubated at 37 ° C. for 40-60 hours. Paclitaxel-loaded polymer nanoparticles, characterized in that 40-60% of the paretictaxel shipped when released. The method of claim 1,
The polymer nanoparticles in which the paclitaxel is shipped,
(Iii) a poly [2- (dimethylamino) ethylmethacrylate-co-methacrylic acid] copolymer and the paclitaxel were mixed and milled to form a complex,
(Ii) Paclitaxel loaded polymer nanoparticles, characterized in that the complex is prepared by dissolving in water and centrifuging. 3. The method of claim 2,
The poly [2- (dimethylamino) ethyl methacrylate-co-methacrylic acid] copolymer is a methacrylic acid (MAA) monomer and 2-dimethylaminoethyl methacrylate (2- (dimethylamino) Ethyl methacrylate, DMAEMA) Paclitaxel-loaded polymer nanoparticles, characterized in that the monomer is prepared by radical polymerization in a nitrogen atmosphere. delete The method of claim 1,
Paclitaxel-loaded polymer nanoparticles, characterized in that the size of the nanoparticles 120-600 nm. A pharmaceutical composition for treating cancer containing the polymer nanoparticles, wherein the paclitaxel shipped according to claim 1 as an active ingredient. delete

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