US-20260124318-A1 - POLYMERIC MATERIAL AND PREPARATION METHOD THEREOF, AND DRUG-LOADING MATERIAL

US20260124318A1US 20260124318 A1US20260124318 A1US 20260124318A1US-20260124318-A1

Abstract

A polymeric material, a preparation method thereof, and a drug-loading material are provided. The polymeric material includes: a crosslinked polymer; and multiple polyelectrolytes, which are grafted onto the three-dimensional network structure of the crosslinked polymer through chemical bonds, each of the polyelectrolytes containing multiple ionizable groups, so that the multiple ionizable groups form local potentials upon ionization to induce aggregation of particles with opposite charges. Compared with conventional drug-loaded microsphere embolic agents, the polymeric material provided by the present disclosure can increase its adsorption amount and adsorption efficiency for particles with opposite charges. When the particles with opposite charges are drug particles, using the polymeric material provided by the present disclosure can increase the drug-loading capacity and shorten the drug-loading time.

Inventors

Qiongyu Guo
Yutao Ma

Assignees

SOUTHERN UNIVERSITY OF SCIENCE AND TECHNOLOGY

Dates

Publication Date: 20260507
Application Date: 20251229
Priority Date: 20230629

Claims (20)

1 . A polymeric material, comprising: a crosslinked polymer; and a plurality of polyelectrolytes grafted via chemical bonds onto a three-dimensional network structure of the crosslinked polymer, wherein each of the polyelectrolytes comprises a plurality of ionizable groups, and the ionizable groups form a local potential after ionization to induce aggregation of particles having an opposite electric charge.
2 . The polymeric material according to claim 1 , wherein each of the polyelectrolytes comprises the plurality of ionizable groups, the plurality of ionizable groups forms a plurality of anionic groups after ionization, and the plurality of anionic groups forms a local low potential capable of inducing aggregation of positively charged particles.
3 . The polymeric material according to claim 1 , wherein each of the polyelectrolytes comprises 3 or more ionizable groups.
4 . The polymeric material according to claim 2 , wherein the ionizable groups comprise at least one of a carboxyl group, a sulfonic acid group, a sulfinic acid group, a phosphoric acid group, a phosphorous acid group, or a hypophosphorous acid group.
5 . The polymeric material according to claim 1 , wherein the polyelectrolytes comprise at least one of polyacrylic acid, carboxymethyl cellulose, carboxymethyl chitosan, sodium alginate, G4 dendrimer, polyglutamic acid, or polyaspartic acid.
6 . The polymeric material according to claim 1 , wherein the crosslinked polymer is a degradable crosslinked polymer.
7 . The polymeric material according to claim 6 , wherein the degradable crosslinked polymer comprises at least one of crosslink-modified gelatin, crosslink-modified chitosan, crosslink-modified hyaluronic acid, crosslink-modified agarose, crosslink-modified chondroitin sulfate, crosslink-modified starch, or crosslink-modified cellulose.
8 . The polymeric material according to claim 1 , wherein the crosslinked polymer accounts for 1-30.% by mass, and the plurality of polyelectrolytes accounts for 0.2-30.% by mass.
9 . The polymeric material according to claim 1 , further comprising: a bridging agent, between the polyelectrolytes and the crosslinked polymer, to connect the polyelectrolytes with the crosslinked polymer.
10 . The polymeric material according to claim 9 , wherein the bridging agent comprises at least two functional groups, and the bridging agent connects the polyelectrolytes with the crosslinked polymer through the at least two functional groups, wherein each of the at least two functional groups comprises any one of an amino group, a carboxyl group, an aldehyde group, a mercapto group, a carbon-carbon double bond, a carbon-carbon triple bond, an acryloyl group, an isobutenoyl group, an azido group, an epoxy group, a vinylsulfonyl group, a succinimide group, a biotin group, a dibenzocyclooctyne group, a di(p-nitrophenyl) carbonate group, or a norbornene group.
11 . A method for preparing a polymeric material, comprising: mixing a crosslinking precursor, a crosslinking agent, and polyelectrolytes; and performing a crosslinking polymerization reaction under an external condition stimulation to form the polymeric material, wherein polymeric material comprises: a crosslinked polymer, and a plurality of the polyelectrolytes grafted via chemical bonds onto a three-dimensional network structure of the crosslinked polymer, wherein each of the polyelectrolytes comprises a plurality of ionizable groups, so that the ionizable groups form a local potential after ionization to induce aggregation of particles having an opposite electric charge.
12 . The preparation method according to claim 11 , wherein the mixing of the crosslinking precursor, the crosslinking agent, and the polyelectrolytes comprises: mixing the crosslinking precursor, the crosslinking agent, the polyelectrolytes, and a bridging agent.
13 . The preparation method according to claim 11 , wherein in the polymeric material, the bridging agent is between the polyelectrolytes and the crosslinked polymer to connect the polyelectrolytes with the crosslinked polymer.
14 . A drug-loading material, comprising: a polymeric material, comprising: a crosslinked polymer, and a plurality of polyions grafted by chemical bonds onto a three-dimensional network structure of the crosslinked polymer; and a plurality of drug particles, adsorbed onto the polymeric material through electrostatic interaction, wherein each of the polyions comprises a plurality of charged groups, and the plurality of charged groups forms a local potential to induce aggregation of the drug particles having opposite electric charges.
15 . The drug-loading material according to claim 14 , wherein the plurality of polyions comprises: a plurality of polyanions, grafted by chemical bonds onto the three-dimensional network structure of the crosslinked polymer; and the plurality of drug particles comprises: a plurality of positively charged drug particles, adsorbed onto the polymeric material through electrostatic interaction, wherein each of the polyanions comprises a plurality of negatively charged groups, and the plurality of negatively charged groups forms a local low potential to induce aggregation of the plurality of positively charged drug particles.
16 . The drug-loading material according to claim 15 , wherein the drug particles are locally aggregated and adsorbed onto the plurality of polyanions of the polymeric material through electrostatic interaction.
17 . The drug-loading material according to claim 16 , wherein the drug particles are further adsorbed, through electrostatic interaction, onto the negatively charged groups carried by the crosslinked polymer.
18 . The drug-loading material according to claim 14 , wherein the drug particles comprise at least one of doxorubicin hydrochloride, epirubicin, mitomycin, fluorouracil, cisplatin, oxaliplatin, capecitabine, gemcitabine, irinotecan, topotecan, sorafenib, apatinib, lenvatinib, regorafenib, cabozantinib, ramucirumab, nivolumab, and pembrolizumab.
19 . The drug-loading material according to claim 14 , wherein the polymeric material further comprises a bridging agent to connect the polyanions with the crosslinked polymer.
20 . The drug-loading material according to claim 19 , wherein the bridging agent comprises at least two functional groups, and the bridging agent connects the polyelectrolytes with the crosslinked polymer through the at least two functional groups, wherein each of the at least two functional groups comprises any one of an amino group, a carboxyl group, an aldehyde group, a mercapto group, a carbon-carbon double bond, a carbon-carbon triple bond, an acryloyl group, an isobutenoyl group, an azido group, an epoxy group, a vinyl sulfone group, a succinimide group, a biotin group, a dibenzocyclooctyne group, a di(p-nitrophenyl)carbonate group, or a norbornene group.

Description

RELATED APPLICATIONS This application is a Continuation-in-Part (CIP) application of PCT application No. PCT/CN2024/111441, filed on August 12, 2024, which claims the benefit of priority to Chinese Patent Application No. 202310790628.5, filed on June 29, 2023, and the content of which is incorporated herein by reference in entirety. TECHNICAL FIELD The present disclosure relates to the technical field of medical polymer materials, and particularly relates to a polymeric material and a preparation method thereof, and a drug-loading material. BACKGROUND Liver cancer is a common cancer worldwide, and transcatheter arterial chemoembolization (TACE) is the preferred strategy for treating middle and late-stage liver cancer. TACE is a technique in which, under the guidance of medical imaging equipment, a drug-loaded embolic agent is injected via a catheter to a target location; the embolic agent blocks the blood supply, while the drug is released from the embolic agent to achieve the intended therapeutic purpose. It has the advantages of being minimally invasive, accurately positioned, and having few side effects. Embolization therapy has achieved good results in treating malignant tumors, uterine fibroids, hemangiomas, vascular malformations, and hemostasis. In recent years, an increasing number of embolic materials have been approved by the China Food and Drug Administration (CFDA) for clinical embolization of blood vessels, tumors, and other indications, including polyvinyl alcohol particulate embolic agents, polyvinyl alcohol drug-loading embolic microspheres, and medical polyether polyurethane embolic agents. TACE technology can achieve chemotherapy effects while performing embolization treatment. To achieve better embolization-chemotherapy effects, higher requirements are placed on the material properties of the embolic agents. The principle for adsorbing drugs in the current preparation of drug-loading microsphere embolic agents is mainly as follows: by using electrostatic adsorption, acidic groups are modified onto the original materials; after ionization, the acidic groups (such as carboxyl groups, etc.) can carry negative charges, enabling the material to have functions such as drug loading. Clinically used embolic agents include polyvinyl alcohol polymer hydrogel microspheres modified with sulfonic acid groups (DC Bead), polyvinyl alcohol embolic microspheres (Callisphere), and embolic microspheres (Hepasphere), etc. At present, in the modified materials used for drug-loading microspheres, the negatively charged groups within the molecules are distributed irregularly in space. Although the number of negative groups is large, their density is not high, and it takes 30 min to 2 h or even more than 2 h to achieve complete drug loading, resulting in excessively long loading times. Moreover, degradable microspheres that have received increasing attention in recent years are limited by the structures of degradable materials. Due to steric hindrance and other factors, the total amount of negatively charged groups within the modified molecules is limited and irregularly distributed, leading to low drug-loading capacity and the inability to ensure sufficient loading of anticancer drugs for tumor treatment. FIG. 1 shows a schematic diagram of the microstructure of an existing drug-loading microsphere. Using the drug-loading microsphere shown in FIG. 1 as an example, carboxyl groups are grafted onto the framework of the polymer material and are dispersed throughout, presenting an irregular distribution. Even though the framework of the polymer material contains many active sites for grafting carboxyl groups, the density of carboxyl groups on the framework of the polymer material is still relatively low. SUMMARY To solve the problems in the existing technology described above, the main purpose of the present disclosure is to provide a polymeric material and a preparation method thereof, and a drug-loading material. To achieve the above purpose, in a first aspect, the present disclosure provides a polymeric material, including: a crosslinked polymer; and a plurality of polyelectrolytes grafted via chemical bonds onto a three-dimensional network structure of the crosslinked polymer, where each of the polyelectrolytes includes a plurality of ionizable groups, and the ionizable groups form a local potential after ionization to induce aggregation of particles having an opposite electric charge. In a second aspect, the present disclosure provides a method for preparing a polymeric material, including: mixing a crosslinking precursor, a crosslinking agent, and polyelectrolytes; and performing a crosslinking polymerization reaction under an external condition stimulation to form the polymeric material, where polymeric material includes: a crosslinked polymer, and a plurality of the polyelectrolytes grafted via chemical bonds onto a three-dimensional network structure of the crosslinked polymer, where each of the polyelectr