US 12,433,959 B2
Injectable hydrogels for controlled release of immunomodulatory compounds
Gillie A. Roth, Stanford, CA (US); Eric Andrew Appel, Stanford, CA (US); Mark Davis, Stanford, CA (US); Emily C. Gale, Stanford, CA (US); and Santiago Correa, Stanford, CA (US)
Assigned to THE BOARD OF TRUSTEES OF THE LELAND STANFORD JUNIOR UNIVERSITY, Stanford, CA (US)
Appl. No. 17/281,014
Filed by THE BOARD OF TRUSTEES OF THE LELAND STANFORD JUNIOR UNIVERSITY, Stanford, CA (US)
PCT Filed Oct. 1, 2019, PCT No. PCT/US2019/054070
§ 371(c)(1), (2) Date Mar. 29, 2021,
PCT Pub. No. WO2020/072495, PCT Pub. Date Apr. 9, 2020.
Claims priority of provisional application 62/739,587, filed on Oct. 1, 2018.
Prior Publication US 2021/0338801 A1, Nov. 4, 2021
Int. Cl. A61K 9/06 (2006.01); A61K 9/00 (2006.01); A61K 9/51 (2006.01); A61K 39/015 (2006.01); A61K 39/145 (2006.01); A61K 39/21 (2006.01); A61K 39/39 (2006.01); A61K 45/00 (2006.01); A61K 47/38 (2006.01); A61K 47/69 (2017.01); A61P 31/16 (2006.01); A61P 35/00 (2006.01); A61K 39/00 (2006.01)
CPC A61K 47/6937 (2017.08) [A61K 9/06 (2013.01); A61K 39/015 (2013.01); A61K 39/145 (2013.01); A61K 39/21 (2013.01); A61K 39/39 (2013.01); A61P 31/16 (2018.01); A61P 35/00 (2018.01); A61K 2039/54 (2013.01); A61K 2039/55577 (2013.01); A61K 2039/55588 (2013.01); A61K 2039/6093 (2013.01)] 28 Claims
 
1. A method comprising:
administering a vaccine delivery system to a subject, wherein the vaccine delivery system comprises:
a hydrogel comprising a hydrophobically-modified cellulose derivative non-covalently cross-linked with a plurality of poly (ethylene glycol)-block-poly (lactic acid) (PEG-PLA) nanoparticles, wherein the hydrogel comprises about 1 wt % of the hydrophobically-modified cellulose derivative and about 5 wt % of the PEG-PLA nanoparticles;
a first immunomodulatory cargo encapsulated in the hydrogel, the first immunomodulatory cargo comprising an immune-activating compound; and
a second immunomodulatory cargo encapsulated in the hydrogel, the second immunomodulatory cargo comprising an antigen,
wherein when the vaccine delivery system is administered to the subject, the hydrogel forms a depot that is configured to (1) recruit antigen-presenting cells (APCs) to infiltrate into the depot, (2) activate the infiltrating APCs with the immune-activating compound and the antigen while the infiltrating APCs are present within the depot, and (3) allow the activated infiltrating APCs to migrate out of the depot.