EP-4739345-A1 - BORONATED HYDROGELS AND METHODS OF MAKING AND USING THE SAME

Abstract

This disclosure pertains to boronated hydrogel compositions, which comprise a boronated polysaccharide compound that comprises a plurality of boronated moieties covalently linked to a carboxylic-acid-containing polysaccharide along a backbone of the carboxylic-acid-containing polysaccharide. The disclosure also pertains to kits that comprise a reservoir, a boronated hydrogel composition comprising a boronated polysaccharide compound that comprises a plurality of boronated moieties covalently linked to a carboxylic-acid-containing polysaccharide along a backbone of the carboxylic-acid-containing polysaccharide disposed in the reservoir, and a device for administering the boronated hydrogel composition to a subject. The disclosure further pertains to methods of treatment that comprise applying or injecting a boronated hydrogel composition comprising a boronated polysaccharide compound that comprises a plurality of boronated moieties covalently linked to a carboxylic-acid-containing polysaccharide along a backbone of the carboxylic-acid-containing polysaccharide onto or into target cells of a subject and delivering neutron beam radiation to the target cells.

Inventors

• HSU, YEN-HAO
• DELANEY, JOSEPH THOMAS, JR.
• PARISI, Cristian

Assignees

• Boston Scientific Scimed, Inc.

Dates

Publication Date

20260513

Application Date

20240702

Claims (1)

1. BSC File No.23-0117WO01 Atty. Docket No.2001.3156111 CLAIMS: 1. A boronated hydrogel composition comprising a boronated polysaccharide compound that comprises a plurality of boronated moieties that are covalently linked to a carboxylic-acid-containing polysaccharide along a backbone of the carboxylic-acid-containing polysaccharide. 2. The boronated hydrogel composition of claim 1, wherein the boronated moieties are covalently linked to the carboxylic-acid-containing polysaccharide through amide or thioester bonds. 3. The boronated hydrogel composition of claim 1 or claim 2, wherein the carboxylic-acid-containing polysaccharide comprises one or more uronic acid species selected from galacturonic acid, glucuronic acid, and iduronic acid. 4. The boronated hydrogel composition of claim 1 or claim 2, wherein the carboxylic-acid-containing polysaccharide is selected from hyaluronic acid, alginic acid, pectin, agaropectin, carrageenan, gellan gum, gum arabic, guar gum, xanthan gum, and carboxymethyl cellulose. 5. The boronated hydrogel composition of any one of claims 1-4, wherein the boronated moieties are selected from dioxaborolane moieties and dodecaborate moieties. 6. The boronated hydrogel composition of any one of claims 1-5, wherein the boronated moieties comprise residues of primary-amine-substituted boronated compounds. 7. The boronated hydrogel composition of any one of claims 1-5, wherein the boronated moieties comprise residues of aminoalkyl dioxaborolane compounds. 8. The boronated hydrogel composition of any one of claims 1-5, wherein the boronated moieties comprise residues of aminoalkyl phenyl dioxaborolane compounds. BSC File No.23-0117WO01 Atty. Docket No.2001.3156111 9. The boronated hydrogel composition of any one of claims 1-5, wherein the boronated moieties comprise residues of thiol-functionalized dodecaborate compounds. 10. The boronated hydrogel composition of any one of claims 1-9, wherein the boronated polysaccharide is covalently crosslinked. 11. The boronated hydrogel composition of any one of claims 1-9, wherein the boronated polysaccharide is ionically crosslinked by multivalent cations. 12. A kit comprising (a) a reservoir, (b) a boronated hydrogel composition in accordance with any one of claims 1-11 disposed in the reservoir, and (c) a device for administering the boronated hydrogel composition to a subject. 13. The kit of claim 12, wherein the reservoir is a syringe barrel. 14. A method of treatment comprising applying or injecting a boronated hydrogel composition in accordance with any one of claims 1-11 onto or into target cells of a subject and delivering neutron beam radiation to the target cells. 15. The method of claim 14, wherein the target cells are surface cancer cells.

Description

BSC File No.23-0117WO01 Atty. Docket No.2001.3156111 BORONATED HYDROGELS AND METHODS OF MAKING AND USING THE SAME CROSS REFERENCE TO RELATED APPLICATIONS [0001] This application claims the benefit of U.S. Provisional Patent Application Serial No.63/525,233 filed on July 6, 2023, the disclosure of which is incorporated herein by reference. FIELD [0002] The present disclosure relates to boronated hydrogels and to methods of making and using such hydrogels, among other aspects. The boronated hydrogels of the present disclosure are useful in biomedical applications, including boron neutron capture therapy. BACKGROUND [0003] Boron neutron capture therapy (BNCT) is a promising and efficient tool whereby cancers are treated by selectively concentrating boron- compounds close to or in tumor cells and then delivering neutron beam radiation for cancer therapy. Boron neutron capture therapy utilizes boronated agents to preferentially deliver boron-10 atoms to tumors. After undergoing irradiation with neutrons, boron-10 yields litihium-7 and an alpha particle. The alpha particle has a short range, therefore preferentially treats tumor tissues while sparing more distant healthy tissues. More specifically, boron neutron capture therapy is based on nuclear capture and fission that follows irradiation of nonradioactive boron-10 with low thermal neutrons which leads to the production of an alpha particle and a recoiling lithium-7 particle (10B + 1n → [11B]* → 4He2 (α) + 7Li3 + 2.38 MeV). Alpha particles are a form of high linear energy transfer (LET) particles that deposit their energy over <10 μm. For further information, see, e.g., K. Nedunchezhian. et al., Boron neutron capture therapy-a literature review, Journal of clinical and diagnostic research: JCDR, 10(12), ZE01 (2016) and T. D. Malouff et al., Boron neutron capture therapy: A review of clinical applications. Frontiers in oncology, 11, 601820 (2021). BSC File No.23-0117WO01 Atty. Docket No.2001.3156111 [0004] Non-animal stabilized hyaluronic acid (NASHA) is a hyaluronic acid preparation that is produced wholly from non-animal sources and is used to form hydrogels that are suitable for injections and as fillers, with good biocompatibility in several applications. One hyaluronic acid-based hydrogel, available as Barrigel®, is used to minimize radiation-associated side effects during prostate cancer treatment by creating the space in between the prostate and rectum. [0005] There is a need in the biomedical arts for hydrogels that are boronated, rendering them potentially useful for boron neutron capture therapy, for methods of making and using such boronated hydrogels, and for systems for forming such boronated hydrogels. SUMMARY [0006] In some aspects, the present disclosure pertains to boronated hydrogel compositions that comprise a boronated polysaccharide compound that comprises a plurality of boronated moieties covalently linked to a carboxylic- acid-containing polysaccharide along a backbone of the carboxylic-acid- containing polysaccharide. [0007] In some embodiments, the boronated moieties are covalently linked to the carboxylic-acid-containing polysaccharide through amide or thioester bonds. [0008] In some embodiments, which can be used in conjunction with the above aspects and embodiments, the carboxylic-acid-containing polysaccharide comprises one or more uronic acid species selected from galacturonic acid, glucuronic acid, and iduronic acid. [0009] In some embodiments, which can be used in conjunction with the above aspects and embodiments, the carboxylic-acid-containing polysaccharide is selected from hyaluronic acid, alginic acid, pectin, agaropectin, carrageenan, gellan gum, gum arabic, guar gum, xanthan gum, and carboxymethyl cellulose. BSC File No.23-0117WO01 Atty. Docket No.2001.3156111 [0010] In some embodiments, which can be used in conjunction with the above aspects and embodiments, the boronated moieties are selected from dioxaborolane moieties and dodecaborate moieties. [0011] In some embodiments, which can be used in conjunction with the above aspects and embodiments, the boronated moieties comprise residues of primary-amine-substituted boronated compounds. [0012] In some embodiments, which can be used in conjunction with the above aspects and embodiments, the boronated moieties comprise residues of aminoalkyl dioxaborolane compounds. [0013] In some embodiments, which can be used in conjunction with the above aspects and embodiments, the boronated moieties comprise residues of aminoalkyl phenyl dioxaborolane compounds. [0014] In some embodiments, which can be used in conjunction with the above aspects and embodiments, the boronated moieties comprise residues of thiol-functionalized dodecaborate compounds. [0015] In some embodiments, which can be used in conjunction with the above aspects and embodiments, the boronated polysaccharide is covalently crosslinked. [0016] In some embodiments, which can be used in conjunction with the above asp