US 11,752,220 B2
Method of delivering genes and drugs to a posterior segment of an eye
Shyam S. Mohapatra, Lutz, FL (US); Subhra Mohapatra, Lutz, FL (US); and Eleni Markoutsa, Tampa, FL (US)
Assigned to The United States Government as Represented by the Department of Veterans Affair, Washington, DC (US); and University of South Florida, Tampa, FL (US)
Filed by University of South Florida, Tampa, FL (US)
Filed on Aug. 6, 2021, as Appl. No. 17/395,683.
Application 17/395,683 is a division of application No. 16/531,734, filed on Aug. 5, 2019, granted, now 11,110,183.
Claims priority of provisional application 62/714,524, filed on Aug. 3, 2018.
Prior Publication US 2021/0369863 A1, Dec. 2, 2021
Int. Cl. C07H 21/02 (2006.01); A61K 47/69 (2017.01); A61K 47/60 (2017.01); A61P 27/02 (2006.01); A61K 9/00 (2006.01); C12N 15/113 (2010.01); A61K 31/7088 (2006.01); A61K 31/4439 (2006.01); A61K 47/61 (2017.01); A61K 47/62 (2017.01); A61K 47/54 (2017.01)
CPC A61K 47/6935 (2017.08) [A61K 9/0048 (2013.01); A61K 31/4439 (2013.01); A61K 31/7088 (2013.01); A61K 47/549 (2017.08); A61K 47/60 (2017.08); A61K 47/61 (2017.08); A61K 47/62 (2017.08); A61K 47/6951 (2017.08); A61P 27/02 (2018.01); C12N 15/113 (2013.01); C12N 2310/122 (2013.01); C12N 2310/14 (2013.01); C12N 2310/351 (2013.01); C12N 2310/531 (2013.01); C12N 2320/31 (2013.01); C12N 2320/32 (2013.01)] 6 Claims
 
1. A method of delivering pioglitazone to a posterior segment of an eye of a patient comprising:
providing a composition comprising
a pharmaceutically acceptable carrier; and
at least one dendrimer-based nanoparticle (MDN) comprising
at least one modified polyamidoamine (PAMAM) dendrimer nanoparticle modified by using molecular extrusion to remove large particles and aggregates to obtain a size of about 10 nm;
at least one short hairpin RNA (shRNA)-encoding DNA molecule complexed to an outer surface of the at least one modified PAMAM dendrimer nanoparticle;
at least one natural cyclodextrin encapsulating the pioglitazone on the outer surface of the at least one modified PAMAM dendrimer nanoparticle; and
a targeting agent targeting a CD44 receptor conjugated to the outer surface of the at least one modified PAMAM dendrimer nanoparticle wherein the targeting agent is selected from the group consisting of hyaluronic acid, cholera toxin B domain, arginylglycylaspartic acid (RGD) peptide, and Tat peptide; and
topically administering the composition to the eye of the patient;
wherein the composition targets the posterior segment of the eye of the patient.