US 11,938,228 B2
Particle-based multi-layer therapeutic delivery device and method
Manijeh Nazari Goldberg, Newburyport, MA (US); Brandon LaPorte, Methuen, MA (US); Aaron Manzi, Atkinson, NH (US); and Amritpreet Birdi, Peabody, MA (US)
Assigned to PRIVO TECHNOLOGIES, INC., Peabody, MA (US)
Filed by Privo Technologies, Inc., Peabody, MA (US)
Filed on Jan. 7, 2019, as Appl. No. 16/241,408.
Application 16/241,408 is a division of application No. 15/932,315, filed on Feb. 16, 2018, abandoned.
Claims priority of provisional application 62/460,665, filed on Feb. 17, 2017.
Prior Publication US 2019/0142760 A1, May 16, 2019
This patent is subject to a terminal disclaimer.
Int. Cl. A61K 9/70 (2006.01); A61K 9/00 (2006.01); A61K 9/107 (2006.01); A61K 9/16 (2006.01); A61K 9/20 (2006.01); A61K 9/24 (2006.01); A61K 31/616 (2006.01); A61K 47/02 (2006.01); A61K 47/36 (2006.01); A61K 47/38 (2006.01)
CPC A61K 9/70 (2013.01) [A61K 9/0014 (2013.01); A61K 9/006 (2013.01); A61K 9/107 (2013.01); A61K 9/167 (2013.01); A61K 9/2077 (2013.01); A61K 9/2086 (2013.01); A61K 9/209 (2013.01); A61K 31/616 (2013.01); A61K 47/02 (2013.01); A61K 47/36 (2013.01); A61K 47/38 (2013.01)] 7 Claims
 
1. A device for delivery of a first therapeutic agent and a second therapeutic agent to a site in epithelial tissue, the device comprising:
a first layer comprising:
a first porous, mucoadhesive, freeze-dried polymeric matrix having first and second opposed surfaces, the first matrix formed by a composition comprising chitosan, a hydration promoter, a particle adhesion inhibitor comprising hydroxypropylmethylcellulose (HPMC), a particle aggregation inhibitor in a concentration from 1% to 10% by weight of the first layer, and a free amount of the first therapeutic agent,
wherein the hydration promoter is selected from the group consisting of ethylene glycol, propylene glycol, beta-propylene glycol, and combinations thereof,
wherein the particle aggregation inhibitor is sucralose, and
a plurality of first particles embedded within the first matrix so as to be directly surrounded by, and in contact with, the first matrix, the first particles encapsulating the first therapeutic agent and comprising chitosan so as to provide controlled release of the first therapeutic agent from the first particles through one of the opposed surfaces of the first matrix, wherein the average diameter of the plurality of first particles is from about 500 nm to about 2000 nm; the first particles further comprising sodium tripolyphosphate, and
a second layer, adjacent to the first layer, the second layer comprising:
a second, freeze-dried polymeric matrix having third and fourth opposed surfaces, the second matrix formed by a composition comprising chitosan and a plurality of second particles embedded within the second matrix, wherein the second particles comprise the second therapeutic agent,
wherein the first surface of the first layer is configured to be attached to the site in the epithelial tissue,
wherein the second surface of the first layer is attached to the third surface of the second layer,
wherein the fourth surface of the second layer is covered with a covering selected from the group consisting of a film, a layer, and a membrane, the covering being configured to restrict passage of any therapeutic agent through the fourth surface of the second layer while still being water permeable, and
wherein at least one of the first therapeutic agent and second therapeutic agent is cisplatin.