MICROCARRIER FOR EMBOLIZATION AND PREPARATION METHOD THEREFOR

Abstract

The present disclosure relates to a microcarrier for embolization, and a preparation method therefor, wherein the microcarrier comprises a biodegradable porous polymer, a stimulus-responsive polymer captured in the biodegradable porous polymer, and drug-supported magnetic nanoparticles captured in the stimulus-responsive polymer, thereby being capable of operating in an in vivo tumor-targeting manner and releasing, by an external stimulus, the drug-supported nanoparticles, so as to be effectively usable in tumor embolization.

Claims

1. A microcarrier, comprising: a biodegradable porous polymer; a stimulus-responsive polymer captured by the biodegradable porous polymer; and drug-loaded magnetic nanoparticles entrapped within the stimulus-responsive polymer.

2. The microcarrier of claim 1, wherein the biodegradable porous polymer is at least one selected from the group consisting of PLGA (poly(lactic-co-glycolic acid)), PGA (poly(glycolic acid)), PLA (poly(lactic acid)), PEG (Polyethylene glycol), collagen, hyaluronic acid, gelatin, and chitosan.

3. The microcarrier of claim 1, wherein the stimulus-responsive polymer is at least one selected from the group consisting of gelatin, PCL (polycaprolactone), chitosan, PNIPAAm (poly(N-isopropylacrylamide)), and HEMA (2-hydroxyethyl(methacrylate)).

4. The microcarrier of claim 1, wherein the magnetic nanoparticles are made from at least one selected from the group consisting of Fe, Co, Mn, Ni, Gd, Mo, MM′.sub.2O.sub.4, M.sub.xO.sub.y (M and M′ are each independently Fe, Co, Ni, Mn, Zn, Gd, or Cr, x is an integer of 1 to 3, and y is an integer of 1 to 5), CoCu, CoPt, FePt, CoSm, NiFe, and NiFeCo.

5. The microcarrier of claim 1, wherein the magnetic nanoparticles are coated with a surface coating agent.

6. The microcarrier of claim 5, wherein the surface coating agent is at least one selected from the group consisting of starch, polyethylenimine, dextran, citrate, carboxydextran, PEG (polyethyleneglycol), and derivatives thereof.

7. The microcarrier of claim 1, wherein the drug is at least one selected from the group consisting of doxorubicin, epirubicin, qemcitabine, cisplatin, carboplatin, procarbazine, cyclophosphamide, dactinomycin, daunorubicin, etoposide, tamoxifen, mitomycin, bleomycin, plicamycin, transplatinum, vinblastine, and methotrexate.

8. An anticancer pharmaceutical composition comprising the microcarrier of claim 1.

9. The anticancer pharmaceutical composition of claim 8, wherein the anticancer pharmaceutical composition is for use in tumor embolization.

10. A method for preparation of a microcarrier, the method comprising: a first loading step of loading a drug onto magnetic nanoparticles; a second loading step of loading magnetic nanoparticles into a stimulus-responsive polymer; and a third loading step of loading the stimulus-responsive polymer into a biodegradable porous polymer.

11. The method of claim 10, wherein the third loading step is carried out by emulsification using a fluidic device.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0076] FIGS. 1a, 1b and 1c are photographic images of the microcarriers according to an embodiment of the present disclosure, taken by an optical microscope (Eclipse Ti-U, Nikon, Japan).

[0077] FIG. 1d is a photographic image of the microcarriers according to an embodiment of the present disclosure, observed with the naked eye.

[0078] FIG. 2 shows results of a magnetic operation experiment performed on the microcarriers according to an embodiment of the present disclosure.

[0079] FIGS. 3a and 3b show results of an experiment of releasing magnetic nanoparticles from the microcarriers according to an embodiment of the present disclosure.

BEST MODE FOR CARRYING OUT THE DISCLOSURE

[0080] A microcarrier, comprising: a biodegradable porous polymer; a stimulus-responsive polymer captured by the biodegradable porous polymer; and drug-loaded magnetic nanoparticles entrapped within the stimulus-responsive polymer.

DETAILED DESCRIPTION

[0081] Hereinafter, the present disclosure will be described in more detail through examples. The following examples are for illustrative purposes only and it will be apparent to those of ordinary skill in the related art that the scope of this disclosure is not limited by the examples.

Preparation Example: Preparation of Microcarrier

[0082] A. Fabrication of Fluidic Device

[0083] Two-way flow channels were constructed by inserting 21G needles into PVC tubes (inner diameter 1/32 inches×outer diameter 3/32 inches) and then equipped with a syringe pump to fabricate a fluidic device for preparation of microcarriers.

[0084] B. Preparation of Microcarrier

[0085] A PLGA solution containing PLGA (poly(lactic-co-glycolic acid), 70 mg/ml) in 1 ml of DCM/Span80 (100:1, v/v) and a gelatin solution containing gelatin (200 mg/ml) and Fe.sub.3O.sub.4 nanoparticles (fluidMAG-D, Chemicell, Germany; 10 mg/mL) in 100 ml of 1% PVA (polyvinyl alcohol) were prepared. Next, the PLGA solution (1 ml) was mixed with the gelatin solution (0.8 ml) (2,500 rpm, 2.5 min) to give a W-O emulsion which was then poured into a 26G needle syringe and inserted into the center of each of the 21G needles in the fluidic device fabricated above (solution: PVA 1%, flow rate: 3 ml/min). The W-O-W droplets formed in the channels were introduced along the 21G needles in the fluidic device and collected in a deionized water-filled 500-ml beaker in an ice bath. The DCM (dichloromethane) entrapped within the collected W-O-W droplets were evaporated by gently stirring for 6 hours. Finally, the DCM-depleted W-O-W droplets (microcarriers) were washed three times with deionized water and stored in a 25-ml vial containing deionized water.

[0086] The microcarriers thus prepared were observed under an optical microscope (Eclipse Ti-U, Nikon, Japan) and the results are depicted in FIGS. 1a to 1c. An image observed with the naked eye is given in FIG. 1d.

Experimental Example 1: Magnetic Operability of Microcarrier

[0087] The microcarriers prepared in the Preparation Example were positioned on a 12-well plate and tested for magnetic mobility by using a neodymium permanent magnet (10 mm in diameter and 5 mm in thickness, N35 grade, JL Magnet, Korea). The result is depicted in FIG. 2.

[0088] As can be seen in FIG. 2, the microcarriers were attracted toward the permanent magnet by the magnetic field generated by the permanent magnet as the magnet approached the microcarriers.

Experimental Example 2: Release of Magnetic Nanoparticle from Microcarrier

[0089] The microcarriers prepared in the Preparation Example were positioned on a 12-well plate and incubated for 30 min in a 37° C. chamber before the release of magnetic nanoparticles was observed by photography (EOS 600D, CANON, Japan) and microscopy (Eclipse Ti-U, Nikon, Japan). The results are depicted in FIGS. 3a and 3b.

[0090] As can be seen in FIG. 3a, the PBS solution containing microcarriers did not change in color before temperature stimulation, but underwent a color change after 30 min of temperature stimulation, implying that the stimulus-responsive polymer (gelatin) is dissolved to release the magnetic nanoparticles from the microcarriers.

[0091] In addition, as shown in FIG. 3b, there is a difference in the transmittance of the microcarrier before and after temperature stimulation, indicating the release of magnetic nanoparticles from the microcarrier, as well.

INDUSTRIAL APPLICABILITY

[0092] The present disclosure relates to a microcarrier for embolization and a preparation method therefor.