# US 10,478,398 B2 · Sol-gel phase-reversible hydrogel templates and uses thereof

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- Number: US 10,478,398 B2
- Document ID: US10478398B2
- Status: Granted
- Kind: B2
- Application number: 15/872,895
- Filed: 2018-01-16
- Published: 2018-08-09
- Granted: 2019-11-19
- Earliest claimed: 2007-09-27
- Assignees: Akina, Inc.
- Applicants: Akina, Inc.
- Inventors: Kinam Park; Ghanashyam S. Acharya; Haesun Park
- Web page: https://patentgrep.com/patent/US10478398B2

## CPC

- A61K 9/1682: {Processes}
- A61K 9/1647: {Polyesters, e.g. poly(lactide-co-glycolide)}
- A61K 9/5031: {obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poly(lactide-co-glycolide)}
- A61K 9/5089: {Processes}
- A61K 31/00: Medicinal preparations containing organic active ingredients
- Y10S 977/773: Nanoparticle, i.e. structure having three dimensions of 100 nm or less
- Y10S 977/887: Nanoimprint lithography, i.e. nanostamp
- Y10S 977/89: Deposition of materials, e.g. coating, cvd, or ald
- Y10S 977/906: Drug delivery
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- Y10S: TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS

## Abstract

Discrete microstructures of predefined size and shape are prepared using sol-gel phase-reversible hydrogel templates. An aqueous solution of hydrogel-forming material is covered onto a microfabricated silicon wafer master template having predefined microfeatures, such as pillars. A hydrogel template is formed, usually by lowering the temperature, and the formed hydrogel template is peeled away from the silicon master template. The wells of predefined size and shape on the hydrogel template are filled with a solution or a paste of a water-insoluble polymer, and the solvent is removed to form solid structures. The formed microstructures are released from the hydrogel template by simply melting the hydrogel template in water. The microstructures are collected by centrifugation. The microstructures fabricated by this method exhibit pre-defined size and shape that exactly correspond to the microwells of the hydrogel template. The method of preparing microstructures based on hydrogel templates is simple and can easily produce large quantities of the microstructures.

## Claims

### Claim 1

A method of making drug-containing microparticles comprising:
(a) filling a plurality of wells provided in a preformed, dissolvable hydrogel mold with a non-aqueous composition comprising: at least one drug, a non-water soluble, biodegradable polymer comprising poly(lactic co-glycolic acid) polymer (PLGA) and non-aqueous solvent, which dissolvable hydrogel mold is formed of a sol-gel phase reversible hydrogel comprising gelatin;
(b) solidifying the composition in the plurality of wells by evaporating the non-aqueous solvent, thereby forming microparticles; and
(c) harvesting the microparticles from the preformed dissolvable hydrogel mold by dissolving the hydrogel mold in an aqueous solution.

### Claim 2 (depends on 1)

The method of claim 1, wherein the drug is present in the microparticles in the range of about 1-80% by weight.

### Claim 3 (depends on 1)

The method of claim 1, wherein the drug is present in the microparticles in the range of about 5-50% by weight.

### Claim 4 (depends on 1)

The method of claim 1, wherein the microparticles have a diameter in the range of about 0.5 μm to about 100 μm.

### Claim 5 (depends on 1)

The method of claim 1, wherein the microparticles have a diameter in the range of about 1 μm to about 50 μm.

### Claim 6 (depends on 1)

The method of claim 1, wherein the harvesting step further comprises filtering and/or centrifugation of the microparticles from the aqueous solution.

### Claim 7 (depends on 1)

The method of claim 1, wherein the harvested microparticles are of homogeneous size.

### Claim 8 (depends on 1)

The method of claim 1, wherein the harvested microparticles are of homogeneous shape.

### Claim 9 (depends on 1)

The method of claim 1, wherein the sol-gel phase reversible hydrogel comprises poly(vinyl alcohol).